Journal Articles

Subclinical cholestasis is a hallmark of gut dysbiosis causing resistance to cancer immunotherapy

Anne-Laure Mallard de La Varende (1); Ai-Ling Tian,1 Simon Thomas (1); Imran Lahmar (1); Meriem Messaoudene (2); Sijing Li (3); Omar Motiño (3,4); Hortense Guillaume-dit-Taunière (1); Valerio Iebba (1); Yoan Hurtado (1); Thao-Nguyen Pham (1); Cassandra Thélémaque (1); Miguel Araujo-Voces (1); Deborah Suissa (1); Pierre Ly (1); Ella Reich (1); Giacomo Vitali (5); Bryan Thierry Arlunno (1); Sylvere Durand (6); Fanny Aprahamian (6); Marion Leduc (3,6); Sabrina Forveille (3,6); Oliver Kepp (3,6); Carlos de la Calle-Fabregat (7); Angela Schippers (8); Norbert Wagner (8); Pierre-Edouard Fournier (9); Kenya Honda (10,11,12); Federica Marmorino (13); Chiara Cremolini (13,14); Saman Maleki Vareki (15,16,17,18).

Cancer Cell

Anne-Laure Mallard de La Varende (1); Ai-Ling Tian,1 Simon Thomas (1); Imran Lahmar (1); Meriem Messaoudene (2); Sijing Li (3); Omar Motiño (3,4); Hortense Guillaume-dit-Taunière (1); Valerio Iebba (1); Yoan Hurtado (1); Thao-Nguyen Pham (1); Cassandra Thélémaque (1); Miguel Araujo-Voces (1); Deborah Suissa (1); Pierre Ly (1); Ella Reich (1); Giacomo Vitali (5); Bryan Thierry Arlunno (1); Sylvere Durand (6); Fanny Aprahamian (6); Marion Leduc (3,6); Sabrina Forveille (3,6); Oliver Kepp (3,6); Carlos de la Calle-Fabregat (7); Angela Schippers (8); Norbert Wagner (8); Pierre-Edouard Fournier (9); Kenya Honda (10,11,12); Federica Marmorino (13); Chiara Cremolini (13,14); Saman Maleki Vareki (15,16,17,18).

Cancer Cell

ABSTRACT: Gut dysbiosis compromises cancer immunosurveillance by downregulating ileal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but the metabolic landscape associated with gut dysbiosis remains elusive. Here, we show that antibiotics (ABX) or ABX-associated Enterocloster species lead to the loss of secondary bile acids (BAs) including deoxycholic acid (DCA) and the accumulation of tauro-conjugated primary BAs (tauro-chenodeoxycholic acid [TCDCA] and tauro-β-muricholic acid [T-βMCA]) from the alternative pathway in the plasma of patients and mice. Fecal microbial transplantation (FMT), the ileum-specific farnesoid X receptor (FXR) agonist fexaramine, or glycodeoxycholic acid (GDCA) compen- sated dysbiosis-associated BA abnormalities and circumvent primary resistance to PD-1 blockade. GDCA curtailed ABX-induced MAdCAM-1 downregulation and T cell exhaustion in tumors. Subclinical cholestasis defined by elevation of γ-glutamyl transferase (γGT) correlated with increased TCDCA and decreased sMAdCAM-1 in plasma and predicted poor survival in multivariate analyses in six cohorts of patients who received immunotherapy. Hence, subclinical cholestasis accompanies gut dysbiosis, paving the way to immunoresistance.

Author Info: 1- Université Paris-Saclay, Gustave Roussy (GRCC), ClinicObiome, Inserm UMR1367, Microbiota and Mucosal Immunity for Cancer Immunotherapy, 94805 Villejuif, France. 2- Centre de rec

Author Info: 1- Université Paris-Saclay, Gustave Roussy (GRCC), ClinicObiome, Inserm UMR1367, Microbiota and Mucosal Immunity for Cancer Immunotherapy, 94805 Villejuif, France. 2- Centre de recherche Du CHUM (CRCHUM), Montréal, QC H2W1T8, Canada. 3- Centre de Recherche des Cordeliers, INSERM U1138, Equipe Labellisée – Ligue Nationale Contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France. 4- Unidad de Excelencia, Instituto de Biomedicina y Genética Molecular de Valladolid, Consejo Superior de Investigaciones Científicas-Universidad de Valladolid, 47001 Valladolid, Spain. 5- MetaGenoPolis, INRAe, Université Paris-Saclay 78350 Jouy en Josas, France. 6- Université Paris-Saclay, INSERM US23, Analyse moléculaire, modélisation et imagerie de la maladie Cancéreuse, Plateformes de Métabolomique et de Criblage Cellulaire Haut Débit, 94805 Villejuif, France. 7- Université Paris-Saclay, Gustave Roussy, U1356 Next Generation Immuno-Oncology Research, 94805 Villejuif, France

Citation: Cancer Cell July 2026

Tags:

    A Patient-Derived Screen Identifies HDAC Inhibitors as Enhancers of Phagocytosis and Potent Immunotherapy Partners

    (1) Khalaj M (2) Burden AT (3) Gutierrez ML (4) Hoonsbeen SC (5) Nejad P (6) Raveh T (7) Young JS (8) Fattahi F (9) Weissman IL

    Cancer immunology research

    (1) Khalaj M (2) Burden AT (3) Gutierrez ML (4) Hoonsbeen SC (5) Nejad P (6) Raveh T (7) Young JS (8) Fattahi F (9) Weissman IL

    Cancer immunology research

    Glioblastoma multiforme (GBM) is a lethal brain tumor with limited treatment options. Tumor-associated macrophages and microglia (TAMs) drive immune suppression and tumor progression, making them a key therapeutic target for GBM. Enhancing TAM phagocytosis in GBM has shown promise, particularly with innate checkpoint inhibitors, such as CD47-blocking antibodies. However, small molecule approaches, which offer tunable and potentially synergistic mechanisms, remain underexplored in this context. In this study, we conducted a large-scale small molecule screen on primary TAMs isolated directly from GBM patient tumors, testing 1,365 compounds to identify drugs that enhance TAM phagocytosis. This screen revealed enrichment for histone deacetylase (HDAC)-targeting drugs among the top hits. HDAC inhibitors enhanced phagocytosis of cancer cells across multiple primary human TAM-GBM combinations, and synergized with CD47 blockade ex vivo. In a xenograft GBM model, Pracinostat suppressed tumor growth and extended survival, with additive benefit when combined with CD47 antibodies. RNA-sequencing and H3K27Ac CUT&Tag profiling of Pracinostat-treated TAMs in vivo revealed a two-tier mechanism: transcriptional reprogramming toward a pro-inflammatory state via NF-_B activation, and epigenetic priming of Fc_R-mediated phagocytic machinery, providing a mechanistic basis for the observed synergy with CD47 blockade. Our findings establish a patient-first functional screening platform for identifying TAM-reprogramming therapeutics in GBM, validate HDAC inhibitors as a lead class that potentiates innate checkpoint immunotherapy, and provide additional candidate compounds for clinical investigation.

    Author Info: (1) Stanford Medicine Stanford United States. ROR: https://ror.org/03mtd9a03 (2) Stanford Medicine United States. ROR: https://ror.org/03mtd9a03 (3) University of California, San F

    Author Info: (1) Stanford Medicine Stanford United States. ROR: https://ror.org/03mtd9a03 (2) Stanford Medicine United States. ROR: https://ror.org/03mtd9a03 (3) University of California, San Francisco San Francisco United States. ROR: https://ror.org/043mz5j54 (4) University of California San Francisco Medical Center San Francisco United States. ROR: https://ror.org/01t8svj65 (5) Stanford Medicine Stanford United States. ROR: https://ror.org/03mtd9a03 (6) Stanford University California 94305-5439, CA United States. ROR: https://ror.org/00f54p054 (7) University of California, San Francisco San Francisco, CA United States. ROR: https://ror.org/043mz5j54 (8) University of California, San Francisco San Francisco, CA United States. ROR: https://ror.org/043mz5j54 (9) Stanford University Stanford University, CA United States. ROR: https://ror.org/00f54p054

    Citation: Cancer Immunol Res 2026 Jul 14 Epub07/14/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42446904

    Tags:

    Dendritic cells control tertiary lymphoid structure development and maintenance in cancer

    (1) Mattiuz R (2) Boumelha J (3) Aerakis E (4) Le Berichel J (5) Hamon P (6) Halasz L (7) Vaidya A (8) Soong BY (9) Radkevich E (10) Kim HM (11) Park MD (12) Donne R (13) Troncoso L (14) Kaplan RA (15) Hennequin C (16) Hern‡ndez-Verdin I (17) L—pez L (18) Rentzeperis F (19) D'Souza D (20) Kaiza ME (21) MacFawn IP (22) Belabed M (23) Mestrallet G (24) Humblin E (25) Merand R (26) Hegde S (27) Lone JC (28) Ioannou G (29) Ozbey S (30) Figueiredo I (31) Tepper A (32) Merarda H (33) Serhan N (34) Schaefer MM (35) An J (36) Ohara RA (37) Nemeth E (38) Goldstein S (39) Reid AM (40) Noureddine M (41) Tabachnikova A (42) Piperno GM (43) Tsoumakidou M (44) Ahmed J (45) Polydorides AD (46) Bhardwaj N (47) Lujambio A (48) Chen Z (49) Gonzalez Kozlova E (50) Kim-Schulze S (51) Brody JD (52) Schotsaert M (53) Moussion C (54) Gnjatic S (55) Roudko V (56) Ginhoux F (57) Murphy KM (58) Sauts-Fridman C (59) Fridman WH (60) Brown BD (61) Marron TU (62) Benvenuti F (63) Cyster JG (64) Salmon H (65) Bruno TC (66) Joshi NS (67) Kamphorst AO (68) Merad M

    Science

    (1) Mattiuz R (2) Boumelha J (3) Aerakis E (4) Le Berichel J (5) Hamon P (6) Halasz L (7) Vaidya A (8) Soong BY (9) Radkevich E (10) Kim HM (11) Park MD (12) Donne R (13) Troncoso L (14) Kaplan RA (15) Hennequin C (16) Hern‡ndez-Verdin I (17) L—pez L (18) Rentzeperis F (19) D'Souza D (20) Kaiza ME (21) MacFawn IP (22) Belabed M (23) Mestrallet G (24) Humblin E (25) Merand R (26) Hegde S (27) Lone JC (28) Ioannou G (29) Ozbey S (30) Figueiredo I (31) Tepper A (32) Merarda H (33) Serhan N (34) Schaefer MM (35) An J (36) Ohara RA (37) Nemeth E (38) Goldstein S (39) Reid AM (40) Noureddine M (41) Tabachnikova A (42) Piperno GM (43) Tsoumakidou M (44) Ahmed J (45) Polydorides AD (46) Bhardwaj N (47) Lujambio A (48) Chen Z (49) Gonzalez Kozlova E (50) Kim-Schulze S (51) Brody JD (52) Schotsaert M (53) Moussion C (54) Gnjatic S (55) Roudko V (56) Ginhoux F (57) Murphy KM (58) Sauts-Fridman C (59) Fridman WH (60) Brown BD (61) Marron TU (62) Benvenuti F (63) Cyster JG (64) Salmon H (65) Bruno TC (66) Joshi NS (67) Kamphorst AO (68) Merad M

    Science

    Tertiary lymphoid structures (TLSs) are associated with immunotherapy response, yet the mechanisms controlling their formation and maintenance remain unclear. Using spatial transcriptomics and multiplex imaging across human tumors, we found that CCR7(+) mature dendritic cells (DCs) accumulate in TLSs. In a mouse non-small cell lung cancer model that forms mature TLSs, we show that early TLS development requires interferon-_ (IFN-_)-driven type 1 conventional dendritic cell (cDC1) maturation, migration to tumor-draining lymph nodes (tdLNs), and T cell recruitment. As tumors progress, TLSs persist independently of tdLN T cell egress, coinciding with cDC1 accumulation within intratumoral CCL19 stromal hubs. There, cDC1-major histocompatibility complex class 1 (MHC-I) and -MHC-II concomitant antigen presentation, along with CD40 signaling, sustain TLS, T follicular helper (T(FH)) cell pool, germinal centers, and tumor-specific immunoglobulin G (IgG). These findings highlight local mature cDC1s as key TLS orchestrators and potential targets to enhance antitumor TLS function.

    Author Info: (1) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn Schoo

    Author Info: (1) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (2) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (3) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Institute for Bioinnovation, "Alexander Fleming" Biomedical Sciences Research Center, Vari, Greece. (4) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (5) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (6) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (7) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (8) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (9) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (10) Tumor Microenvironment Center, Department of Immunology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. (11) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (12) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (13) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (14) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (15) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (16) Department of Immunology, Inflammation, Complement and Cancer, Centre de Recherche des Cordeliers, Sorbonne UniversitŽ, INSERM, UniversitŽ Paris CitŽ, Paris, France. (17) Cellular Immunology, International Centre for Genetic Engineering and Biotechnology, ICGEB, Trieste, Italy. (18) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (19) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (20) Tumor Microenvironment Center, Department of Immunology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. (21) Tumor Microenvironment Center, Department of Immunology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. Department of Biology, Grove City College, Grove City, PA, USA. (22) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (23) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (24) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (25) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (26) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (27) GIMM, Gulbenkian Institute for Molecular Medicine and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. (28) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (29) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (30) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (31) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (32) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (33) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (34) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (35) Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. (36) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. (37) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (38) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (39) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (40) Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health and Emerging Pathogens Institute and Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (41) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (42) Cellular Immunology, International Centre for Genetic Engineering and Biotechnology, ICGEB, Trieste, Italy. (43) Institute for Bioinnovation, "Alexander Fleming" Biomedical Sciences Research Center, Vari, Greece. (44) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (45) Henry D. Janowitz Division of Gastroenterology, Department of Medicine, and Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (46) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (47) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (48) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (49) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (50) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (51) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (52) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. GIMM, Gulbenkian Institute for Molecular Medicine and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. Global Health and Emerging Pathogens Institute and Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (53) Genentech, South San Francisco, CA, USA. (54) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (55) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (56) Paris-Saclay University, Gustave Roussy, INSERM U1015, Villejuif, France. (57) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. (58) Department of Immunology, Inflammation, Complement and Cancer, Centre de Recherche des Cordeliers, Sorbonne UniversitŽ, INSERM, UniversitŽ Paris CitŽ, Paris, France. (59) Department of Immunology, Inflammation, Complement and Cancer, Centre de Recherche des Cordeliers, Sorbonne UniversitŽ, INSERM, UniversitŽ Paris CitŽ, Paris, France. (60) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (61) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Institute for Thoracic Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (62) Cellular Immunology, International Centre for Genetic Engineering and Biotechnology, ICGEB, Trieste, Italy. (63) Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. (64) Institut Curie, Paris, France. (65) Tumor Microenvironment Center, Department of Immunology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. (66) Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. (67) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Graduate Education, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (68) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

    Citation: Science 2026 Jul 16 393:eady1678 Epub07/16/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42462020

    Tags:

    Tryptophan degradation by intestinal Bacteroides induces anti-tumor immunity and limits melanoma growth Spotlight 

    (1) Olea XD (2) Beede K (3) Pereira G (4) Scott D (5) Petucci C (6) Martens E (7) Rodionov D (8) Shah A (9) Martinez MP (10) Kim H (11) Sharma AK (12) Martin A (13) Zhang T (14) Faries MB (15) Hamid O (16) Devkota S (17) Osterman A (18) Knott S (19) Voest EE (20) Ajami NJ (21) Wargo J (22) Ramer-Tait AE (23) Ronai ZA

    Cell reports. Medicine

    Olea and Beede et al. identified Bacteroides rodentium and Bacteroides uniformis (found in mice and humans, respectively) as gut microbes that induced antitumor immunity and inhibited tumor growth in melanoma mouse models. These strains expressed tryptophanase A (TnaA) and aromatic aminotransferases (ArAT) that degraded tryptophan into indoles. TnaA loss in B. uniformis abrogated antitumor activity, whereas indole administration increased CD8+ T cell infiltration and restrained tumor growth, independent of AhR signaling. Elevated levels of ArAT and TnaA were found in patients with melanoma who responded to ICB.

    Contributed by Shishir Pant

    (1) Olea XD (2) Beede K (3) Pereira G (4) Scott D (5) Petucci C (6) Martens E (7) Rodionov D (8) Shah A (9) Martinez MP (10) Kim H (11) Sharma AK (12) Martin A (13) Zhang T (14) Faries MB (15) Hamid O (16) Devkota S (17) Osterman A (18) Knott S (19) Voest EE (20) Ajami NJ (21) Wargo J (22) Ramer-Tait AE (23) Ronai ZA

    Cell reports. Medicine

    Olea and Beede et al. identified Bacteroides rodentium and Bacteroides uniformis (found in mice and humans, respectively) as gut microbes that induced antitumor immunity and inhibited tumor growth in melanoma mouse models. These strains expressed tryptophanase A (TnaA) and aromatic aminotransferases (ArAT) that degraded tryptophan into indoles. TnaA loss in B. uniformis abrogated antitumor activity, whereas indole administration increased CD8+ T cell infiltration and restrained tumor growth, independent of AhR signaling. Elevated levels of ArAT and TnaA were found in patients with melanoma who responded to ICB.

    Contributed by Shishir Pant

    ABSTRACT: Study of gut microbiota control of anti-tumor immunity (ATI) identifies Bacteroides rodentium and the human-related Bacteroides uniformis species to be capable of inducing ATI and limiting melanoma development in germ-free (GF), complex microbiome, or wild-type (WT) mice. Enhanced CD8(+) T cell infiltration within tumors of mice harboring B. rodentium coincides with increased expression of immune-stimulating pathways. Metabolomic analyses identify lower tryptophan levels in the cecal samples of GF mice harboring B. rodentium. In silico genomic reconstruction reveals that B. rodentium and B. uniformis harbor tryptophanase A (TnaA) and aromatic aminotransferase genes, which degrade tryptophan to indoles. Administration of B. uniformis harboring TnaA mutant fails to inhibit melanoma growth. Notably, administration of indoles effectively induces ATI and inhibits melanoma development. Correspondingly, the levels of bacterially encoded tryptophan-degrading enzymes are higher in cohorts of patients with melanoma responding to immunotherapy. These findings identify indoles as tryptophan breakdown products capable of inducing ATI resulting in melanoma inhibition.

    Author Info: (1) Translational Research Institute, Elinor and Rendall Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars S

    Author Info: (1) Translational Research Institute, Elinor and Rendall Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. (2) Department of Food Science and Technology, Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE 68588, USA. (3) Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. (4) Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. (5) Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. (6) Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. (7) Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. (8) Translational Research Institute, Elinor and Rendall Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. (9) Division of Molecular Oncology & Immunology, the Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands. (10) Translational Research Institute, Elinor and Rendall Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. (11) Human Microbiome Research Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. (12) Human Microbiome Research Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. (13) Division of Cancer Epidemiology & Genetics, National Cancer Institute, Rockville, MD 20892, USA. (14) The Angeles Clinic and Research Institute, Cedars Sinai Medical Center, Los Angeles, CA 90025, USA. (15) The Angeles Clinic and Research Institute, Cedars Sinai Medical Center, Los Angeles, CA 90025, USA. (16) Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; Human Microbiome Research Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. (17) Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. (18) Translational Research Institute, Elinor and Rendall Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. (19) Division of Molecular Oncology & Immunology, the Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands. (20) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. (21) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. (22) Department of Food Science and Technology, Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE 68588, USA. Electronic address: aramer-tai2@unl.edu. (23) Translational Research Institute, Elinor and Rendall Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: zeev.ronai@csmc.edu.

    Citation: Cell Rep Med 2026 Jul 14 102921 Epub07/14/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42447866

    Tags:

    Epigenetic landscape, key transcriptional regulators, and in vivo identification of human Tr1 cells Spotlight 

    (1) Cepika AM (2) Amaya L (3) Waichler C (4) Narula M (5) Mantilla M (6) Thomas BC (7) Chen PP (8) Freeborn RA (9) Pavel-Dinu M (10) Nideffer J (11) Porteus M (12) Bacchetta R (13) MŸller F (14) Greenleaf WJ (15) Chang HY (16) Roncarolo MG

    Science advances | Free PMC Article

    Investigating type 1 regulatory CD4+ T (Tr1) cells induced from conventional Foxp3-CD4+ T cells exposed to antigen-presenting tolerogenic DCs and IL-10, Cepika et al. used multiomic profiling and functional genomics to identify IRF4, BATF, and MAF as key transcription factors involved in human Tr1 cell differentiation, phenotype, and function. While Tr1 cells shared some features with Tregs, they showed distinct clonal expansion and functionality. A transcriptional signature for Tr1 cells was defined and successfully identified Tr1 cells in data from Tr1 therapy (T-allo10)-treated patient peripheral blood, high-TMB solid human tumors, and mice treated with a high-dose neoantigen vaccine.

    Contributed by Lauren Hitchings

    (1) Cepika AM (2) Amaya L (3) Waichler C (4) Narula M (5) Mantilla M (6) Thomas BC (7) Chen PP (8) Freeborn RA (9) Pavel-Dinu M (10) Nideffer J (11) Porteus M (12) Bacchetta R (13) MŸller F (14) Greenleaf WJ (15) Chang HY (16) Roncarolo MG

    Science advances | Free PMC Article

    Investigating type 1 regulatory CD4+ T (Tr1) cells induced from conventional Foxp3-CD4+ T cells exposed to antigen-presenting tolerogenic DCs and IL-10, Cepika et al. used multiomic profiling and functional genomics to identify IRF4, BATF, and MAF as key transcription factors involved in human Tr1 cell differentiation, phenotype, and function. While Tr1 cells shared some features with Tregs, they showed distinct clonal expansion and functionality. A transcriptional signature for Tr1 cells was defined and successfully identified Tr1 cells in data from Tr1 therapy (T-allo10)-treated patient peripheral blood, high-TMB solid human tumors, and mice treated with a high-dose neoantigen vaccine.

    Contributed by Lauren Hitchings

    ABSTRACT: Type 1 regulatory T (Tr1) cells are CD4(+) T cells with suppressive function that are induced from conventional T cells exposed to persistent or strong antigens. Human Tr1 cells are understudied; the regulators of their antigen-driven differentiation are unknown, and identifying them in tissues, where antigen interactions occur, is challenging. Here, we conducted a multiomic profiling of human antigen-induced Tr1 cells. Using CRISPR-based functional genomics, we uncovered essential roles of transcription factors IRF4, BATF, and MAF in human Tr1 differentiation, phenotype, and function. We also derived a Tr1 transcriptional signature that detects cells with a Tr1 phenotype in single-cell datasets from patients treated with Tr1 therapy and those with solid tumors. Cross-species analysis confirmed this signature identifies bona fide Tr1 cells induced in vivo in a murine solid tumor model. These findings provide a framework for development of Tr1-based and Tr1-targeting therapies and studies of Tr1 cell biology.

    Author Info: (1) Division of General Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. Division of Hematology, Oncology, Stem Cell Transplantation and R

    Author Info: (1) Division of General Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. Center for Definitive and Curative Medicine, Stanford University School of Medicine, Stanford, CA, USA. (2) Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA. (3) Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. (4) Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. (5) Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. (6) Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. (7) Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. (8) Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. (9) Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. Division of Immunology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA. (10) Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA, USA. (11) Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. Center for Definitive and Curative Medicine, Stanford University School of Medicine, Stanford, CA, USA. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. (12) Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. Center for Definitive and Curative Medicine, Stanford University School of Medicine, Stanford, CA, USA. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. (13) Integrative Cellular Biology and Bioinformatics, Saarland University, SaarbrŸcken, Germany. Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. (14) Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. (15) Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. Center for Personal Dynamic Regulome, Stanford University School of Medicine, Stanford, CA, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. (16) Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. Center for Definitive and Curative Medicine, Stanford University School of Medicine, Stanford, CA, USA. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.

    Citation: Sci Adv 2026 Jul 10 12:eaec6358 Epub07/10/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42430483

    Tags:

    The CARM1 epigenetic enzyme inhibits cross-presenting dendritic cell function in cancer immunity Featured  

    (1) Zhang X (2) Xirenayi S (3) Zhao Y (4) Wang W (5) Han Y (6) Sobral M (7) Kang S (8) Zhang C (9) Barlow GL (10) Pyrdol J (11) Cho JW (12) Huang K (13) Ning X (14) Hemberg M (15) Yuan GC (16) Van Allen EM (17) Mooney DJ (18) Wucherpfennig KW

    Science

    Zhang et al. investigated the role of the CARM1 in cDC1s and found that while its effect on cDC1s in healthy tissues was minimal, inactivation of Carm1 in tumor cDC1s enhanced their activation and cross-presentation of tumor antigens, resulting in increased CD8+ T cell-mediated antitumor efficacy. Carm1 expression was found to be downregulated by type 1 IFN and TNFα, and upregulated by TGFβ via Smad2/3. CARM1 altered chromatin expression, with its loss leading to enhanced chromatin access at regions associated with NF-κB and AP-1 binding, which supported enhanced activation and antigen presentation. When used in combination with a neoantigen vaccine, inhibition of Carm1 enhanced antitumor responses.

    (1) Zhang X (2) Xirenayi S (3) Zhao Y (4) Wang W (5) Han Y (6) Sobral M (7) Kang S (8) Zhang C (9) Barlow GL (10) Pyrdol J (11) Cho JW (12) Huang K (13) Ning X (14) Hemberg M (15) Yuan GC (16) Van Allen EM (17) Mooney DJ (18) Wucherpfennig KW

    Science

    Zhang et al. investigated the role of the CARM1 in cDC1s and found that while its effect on cDC1s in healthy tissues was minimal, inactivation of Carm1 in tumor cDC1s enhanced their activation and cross-presentation of tumor antigens, resulting in increased CD8+ T cell-mediated antitumor efficacy. Carm1 expression was found to be downregulated by type 1 IFN and TNFα, and upregulated by TGFβ via Smad2/3. CARM1 altered chromatin expression, with its loss leading to enhanced chromatin access at regions associated with NF-κB and AP-1 binding, which supported enhanced activation and antigen presentation. When used in combination with a neoantigen vaccine, inhibition of Carm1 enhanced antitumor responses.

    ABSTRACT: The cancer-immunity cycle requires cross-presenting type I conventional dendritic cells (cDC1s) that induce T cell-mediated immunity, but therapeutic strategies for enhancing intratumoral cDC1 function are currently inadequate. We found the epigenetic enzyme CARM1 (coactivator-associated arginine methyltransferase 1) to be a selective negative regulator of cancer antigen presentation by cDC1s but not cDC2s. Inactivation of the Carm1 gene promoted cDC1 antigen cross-presentation, activation, and accumulation in tumors, and a CARM1 inhibitor enhanced cDC1-mediated priming of T cells by means of a cancer neoantigen vaccine. CARM1 inhibition increased chromatin accessibility at BATF3-Jun and RelA sites that are critical for cDC1 function and activation. Transforming growth factor-β regulated Carm1 expression, which suggests that CARM1 inactivation enhanced intratumoral cDC1 function without altering cDC1 homeostasis. These studies identify CARM1 as a potential therapeutic target for enhancing the antitumor function of mouse and human cDC1s.

    Author Info: (1) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Immunology, Harvard Medical School, Boston, MA, USA. (2) Department o

    Author Info: (1) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Immunology, Harvard Medical School, Boston, MA, USA. (2) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Broad Institute of Harvard and MIT, Cambridge, MA, USA. Systems, Synthetic, and Quantitative Biology Graduate Program, Harvard University, Cambridge, MA, USA. (3) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. (4) Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (5) Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. (6) Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. (7) Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. (8) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Immunology, Harvard Medical School, Boston, MA, USA. (9) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Immunology, Harvard Medical School, Boston, MA, USA. (10) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. (11) Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. (12) Molecular Imaging Core, Dana-Farber Cancer Institute, Boston, MA, USA. (13) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Immunology, Harvard Medical School, Boston, MA, USA. (14) Broad Institute of Harvard and MIT, Cambridge, MA, USA. Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. (15) Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Tisch Cancer Institute, Black Family Stem Cell Institute, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (16) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Broad Institute of Harvard and MIT, Cambridge, MA, USA. Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA. (17) Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. (18) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Immunology, Harvard Medical School, Boston, MA, USA. Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.

    Citation: Science 2026 Jul 9 393:eaea1200 Epub07/09/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42424445

    Tags:

    Generalizable AI predicts immunotherapy outcomes across cancers and treatments Spotlight 

    (1) Shen W (2) Moon I (3) Nguyen TH (4) Li MM (5) Huang Y (6) Nair N (7) Marbach D (8) Zitnik M

    Nature medicine

    Shen et al. developed COMPASS, an AI model that interprets pre-treatment tumor RNAseq data in the context of tumor-immune gene expression modules and maps them to predict ICB response. Trained on TCGA and cohort data, COMPASS was applicable across cohorts, indications, ICB drugs, and targets, with superior response prediction compared to established models or correlates (TMB, PD-L1). COMPASS also generated personalized “response maps” identifying potential resistance mechanisms; unexpected nonresponders (i.e. patients with an inflammatory TME) often had gene expression associated with angiogenesis, TGFβ, and B cell deficiency.

    Contributed by Alex Najibi

    (1) Shen W (2) Moon I (3) Nguyen TH (4) Li MM (5) Huang Y (6) Nair N (7) Marbach D (8) Zitnik M

    Nature medicine

    Shen et al. developed COMPASS, an AI model that interprets pre-treatment tumor RNAseq data in the context of tumor-immune gene expression modules and maps them to predict ICB response. Trained on TCGA and cohort data, COMPASS was applicable across cohorts, indications, ICB drugs, and targets, with superior response prediction compared to established models or correlates (TMB, PD-L1). COMPASS also generated personalized “response maps” identifying potential resistance mechanisms; unexpected nonresponders (i.e. patients with an inflammatory TME) often had gene expression associated with angiogenesis, TGFβ, and B cell deficiency.

    Contributed by Alex Najibi

    ABSTRACT: Immune checkpoint inhibitors (ICIs) are a standard treatment across cancers, yet most patients do not respond, and existing biomarkers generalize poorly across tumor types and therapies. Here we present COMPASS, a pan-cancer foundation model that predicts immunotherapy response from bulk tumor transcriptomes using a concept bottleneck transformer. COMPASS encodes gene expression through 44 biologically grounded immune concepts representing immune cell states, tumor-microenvironment interaction and signaling pathways. Trained on 10,184 tumors across 33 cancer types, COMPASS achieves better average performance than 22 methods across 16 clinical cohorts spanning seven cancers and six ICIs, improving accuracy by 8.5% and area under the precision-recall curve by 15.7% on average across cohorts. COMPASS generalizes to cancer types and treatments not represented during fine-tuning and may inform indication selection and patient stratification. In survival analyses, patients classified by COMPASS as responders had longer overall survival (hazard ratio_=_4.7, P_<_0.0001). Personalized response maps connect gene expression to immune concepts, identifying programs associated with response and resistance; in immune-inflamed non-responders, COMPASS highlights programs including TGF_ signaling, endothelial exclusion, CD4(+) T cell dysfunction and B cell deficiency. COMPASS predicts immunotherapy response and provides hypothesis-generating mechanistic insight for trial design and translational studies.

    Author Info: (1) Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. (2) Department of Biome

    Author Info: (1) Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. (2) Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. (3) Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. (4) Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. (5) Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. (6) Roche Pharma Research and Early Development, Oncology Early Clinical Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland. (7) Computational Sciences Center of Excellence, F. Hoffmann-La Roche Ltd., Basel, Switzerland. daniel.marbach.dm1@roche.com. (8) Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. marinka@hms.harvard.edu. Kempner Institute for the Study of Natural and Artificial Intelligence, Harvard University, Allston, MA, USA. marinka@hms.harvard.edu. Broad Institute of MIT and Harvard, Cambridge, MA, USA. marinka@hms.harvard.edu. Harvard Data Science Initiative, Cambridge, MA, USA. marinka@hms.harvard.edu.

    Citation: Nat Med 2026 Jul 3 Epub07/03/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42399673

    Tags:

    Single-cell transcriptomic analysis reveals tumor-immune determinants of lymph node colonization and progression in thyroid cancer Spotlight 

    (1) Nguyen AT (2) Viramontes J (3) Vazquez I (4) McWilliam C (5) Devarakonda V (6) Henson R (7) Sacks WL (8) Mallen-St Clair J (9) Chen Y (10) Walgama E (11) Scher KS (12) Moyers J (13) Sandler HM (14) Jang JK (15) Zumsteg ZS (16) Shon W (17) Shiao SL (18) Ho AS

    Science advances | Free PMC Article

    Nguyen et al. used single-cell RNAseq and multiplex IHC on paired primary thyroid carcinomas and metastatic lymph nodes (LNs) to define immune determinants of nodal colonization. In metastatic LNs, thyrocytes and TAMs downregulated inflammatory cytokine receptors. including TNFRSF12A and CX3CR1, and were enriched for Tregs relative to matched primary tumors, which suggests suppression of T cell-mediated cytotoxicity. Tumor-infiltrating lymphocytes in metastatic LNs showed increased IL7R expression, and high IL7R levels within nodal metastases correlated with enhanced immune activation and improved progression-free survival in a validation cohort.

    Contributed by Shishir Pant

    (1) Nguyen AT (2) Viramontes J (3) Vazquez I (4) McWilliam C (5) Devarakonda V (6) Henson R (7) Sacks WL (8) Mallen-St Clair J (9) Chen Y (10) Walgama E (11) Scher KS (12) Moyers J (13) Sandler HM (14) Jang JK (15) Zumsteg ZS (16) Shon W (17) Shiao SL (18) Ho AS

    Science advances | Free PMC Article

    Nguyen et al. used single-cell RNAseq and multiplex IHC on paired primary thyroid carcinomas and metastatic lymph nodes (LNs) to define immune determinants of nodal colonization. In metastatic LNs, thyrocytes and TAMs downregulated inflammatory cytokine receptors. including TNFRSF12A and CX3CR1, and were enriched for Tregs relative to matched primary tumors, which suggests suppression of T cell-mediated cytotoxicity. Tumor-infiltrating lymphocytes in metastatic LNs showed increased IL7R expression, and high IL7R levels within nodal metastases correlated with enhanced immune activation and improved progression-free survival in a validation cohort.

    Contributed by Shishir Pant

    ABSTRACT: Lymph node (LN) metastases are a major driver of mortality across solid cancers, including thyroid carcinomas, which are known for high rates of nodal colonization. To elucidate the determinants of nodal spread, we isolated tumor-infiltrating leukocytes from primary thyroid tumors and matched metastatic LNs for single-cell RNA sequencing with validation by multiplex immunohistochemistry. Comparing the microenvironmental alterations between primary tumors and their LNs, we found that thyrocytes and tumor-associated macrophages down-regulate the expression of multiple inflammatory cytokine receptors, including TNFRSF12A and CX3CR1, upon LN colonization. LNs were associated with the induction of regulatory T cells to suppress T cell-mediated cytotoxicity compared to matched primary tumors. Notably, tumor-infiltrating lymphocytes within LNs demonstrated increased expression of activation markers, including interleukin-7 receptor (IL7R). High LN expression of IL7R was significantly correlated with improved outcomes and can serve as a biomarker in this heterogeneous disease. Our findings on the dynamic equilibrium within LN metastases may offer conserved mechanisms for nodal colonization across solid tumors.

    Author Info: (1) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA,

    Author Info: (1) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (2) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (3) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (4) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (5) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (6) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (7) Division of Endocrinology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (8) Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (9) Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (10) Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (11) Division of Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (12) Division of Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (13) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (14) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (15) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (16) Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (17) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. (18) Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

    Citation: Sci Adv 2026 Jul 3 12:eaea4727 Epub07/03/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42397917

    Tags:

    Sustained A2AR expression and loss paradoxically promote CD8+ T cell exhaustion

    Spotlight 

    (1) Song L (2) Kharel A (3) Xie P (4) Fan J (5) Baker A (6) Zhang Y (7) Zhang Y (8) Cui W (9) Zhang B

    Proceedings of the National Academy of Sciences of the United States of America | Free PMC Article

    Using single-cell multiomics and genetic models, Song and Kharel et al. showed that, paradoxically, both sustained A2AR expression under chronic antigen exposure and hypoxia, and complete loss of A2AR drive the transition of TCFhi memory-like progenitor (Tpro) cells to exhausted T cells. A2AR expression was rapidly induced upon TCR stimulation and was required to sustain CD8+ T cell functions. Persistent A2AR expression promoted continuous TCR engagement and CD8+ T cell exhaustion via activation of the GαS-cAMP-PKA pathway. A2AR depletion led to epigenetic remodeling and activation of CD122 (IL-2Rβ)-dependent signaling, driving exhaustion.

    Contributed by Ute Burkhardt

    (1) Song L (2) Kharel A (3) Xie P (4) Fan J (5) Baker A (6) Zhang Y (7) Zhang Y (8) Cui W (9) Zhang B

    Proceedings of the National Academy of Sciences of the United States of America | Free PMC Article

    Using single-cell multiomics and genetic models, Song and Kharel et al. showed that, paradoxically, both sustained A2AR expression under chronic antigen exposure and hypoxia, and complete loss of A2AR drive the transition of TCFhi memory-like progenitor (Tpro) cells to exhausted T cells. A2AR expression was rapidly induced upon TCR stimulation and was required to sustain CD8+ T cell functions. Persistent A2AR expression promoted continuous TCR engagement and CD8+ T cell exhaustion via activation of the GαS-cAMP-PKA pathway. A2AR depletion led to epigenetic remodeling and activation of CD122 (IL-2Rβ)-dependent signaling, driving exhaustion.

    Contributed by Ute Burkhardt

    ABSTRACT: Although A2AR is a key immunoregulatory receptor that suppresses CD8(+) T cell activation in response to elevated extracellular adenosine in inflamed or hypoxic microenvironments, its role in CD8(+) T cell differentiation and cell-fate decisions during chronic viral infection and cancer remains poorly understood. Using A2AR-eGFP reporter mice, we show that A2AR expression is rapidly induced by TCR stimulation and persists under chronic antigen exposure and hypoxia, with sustained expression strongly associated with terminal exhaustion via the canonical G_(s)-cAMP-PKA pathway. Paradoxically, A2AR loss does not alleviate exhaustion but instead accelerates differentiation toward the terminally exhausted state. Single-cell multiomics profiling revealed that A2AR deficiency activates CD122 (IL-2R_)-dependent signaling, driving T cell exhaustion. Genetic deletion of CD122 in A2AR-deficient CD8(+) T cells reduced terminal exhaustion, identifying CD122 signaling as a key mediator of A2AR loss-driven exhaustion. Intriguingly, both sustained A2AR expression and A2AR loss converge to promote T cell exhaustion differentiation through distinct mechanisms. These findings uncover a paradoxical role of A2AR in shaping CD8(+) T cell fate choices during chronic infection and cancer.

    Author Info: (1) Department of Medicine and Hematology and Oncology Division, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine Chicago, IL 60611.

    Author Info: (1) Department of Medicine and Hematology and Oncology Division, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine Chicago, IL 60611. ROR: https://ror.org/02p4far57 (2) Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611. (3) Department of Medicine and Hematology and Oncology Division, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine Chicago, IL 60611. ROR: https://ror.org/02p4far57 (4) Department of Medicine and Hematology and Oncology Division, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine Chicago, IL 60611. ROR: https://ror.org/02p4far57 (5) Department of Medicine and Hematology and Oncology Division, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine Chicago, IL 60611. ROR: https://ror.org/02p4far57 (6) Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611. (7) Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. ROR: https://ror.org/056swr059 (8) Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611. (9) Department of Medicine and Hematology and Oncology Division, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine Chicago, IL 60611. ROR: https://ror.org/02p4far57

    Citation: Proc Natl Acad Sci U S A 2026 Jul 7 123:e2602385123 Epub06/30/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42378284

    Tags:

    RIG-I-targeted immunotherapy synergizes with immune checkpoint inhibition in a hepatocellular carcinoma model Spotlight 

    (1) Marx C (2) Teppert J (3) Marisch L (4) Formisano S (5) Senz A (6) Boehmer DFR (7) Metzger P (8) Kechur D (9) Delius L (10) Hoerth C (11) Lauber K (12) Mayr D (13) De Toni EN (14) Helms MW (15) Brunner B (16) Endres S (17) Schnurr M (18) Duewell P (19) Rothenfusser S (20) Koenig LM

    Molecular cancer therapeutics

    Marx, Teppert, and Marisch et al. showed retinoic acid-inducible gene-I (RIG-I), the cytoplasmic sensor of short dsRNA with uncapped 5’-triphosphate (3p-RNA), was expressed in human HCC samples and induced by IFN-I on cell lines. 3p-RNA treatment given i.v. reduced tumor burden in murine orthotopic tumor models and induced immune memory. Therapeutic effects depended on CD4+ and CD8+ T, but not NK cells, and on tumor-intrinsic Fas expression, but not systemic intracellular RIG-I pathway signaling. Treatment with 3p-RNA upregulated PD-L1 expression on HCC cells and synergized with anti-PD-1 to improve efficacy in HCC mouse models.

    Contributed by Paula Hochman

    (1) Marx C (2) Teppert J (3) Marisch L (4) Formisano S (5) Senz A (6) Boehmer DFR (7) Metzger P (8) Kechur D (9) Delius L (10) Hoerth C (11) Lauber K (12) Mayr D (13) De Toni EN (14) Helms MW (15) Brunner B (16) Endres S (17) Schnurr M (18) Duewell P (19) Rothenfusser S (20) Koenig LM

    Molecular cancer therapeutics

    Marx, Teppert, and Marisch et al. showed retinoic acid-inducible gene-I (RIG-I), the cytoplasmic sensor of short dsRNA with uncapped 5’-triphosphate (3p-RNA), was expressed in human HCC samples and induced by IFN-I on cell lines. 3p-RNA treatment given i.v. reduced tumor burden in murine orthotopic tumor models and induced immune memory. Therapeutic effects depended on CD4+ and CD8+ T, but not NK cells, and on tumor-intrinsic Fas expression, but not systemic intracellular RIG-I pathway signaling. Treatment with 3p-RNA upregulated PD-L1 expression on HCC cells and synergized with anti-PD-1 to improve efficacy in HCC mouse models.

    Contributed by Paula Hochman

    ABSTRACT: Retinoic acid-inducible gene-I (RIG-I) is a cytoplasmic pattern recognition receptor that senses short double-stranded RNA with uncapped 5'-triphosphate (3p-RNA). Upon activation, RIG-I induces type I interferons and proinflammatory cytokines, thereby promoting adaptive immunity. Thus, RIG-I activation is a promising approach for creating a proinflammatory tumor microenvironment. In this study, we investigated its therapeutic potential in hepatocellular carcinoma (HCC). We explored and confirmed RIG-I expression and signaling in human HCC samples and cell lines. The therapeutic potential of RIG-I activation by 3p-RNA for the treatment of HCC was investigated in vitro and in syngeneic murine orthotopic tumor models. In vivo, 3p-RNA treatment significantly reduced the tumor burden, delayed disease progression, and achieved partial complete remission of RIL-175 tumors with durable immune memory. However, no therapeutic effects were observed in the Hep-55.1C model. Tumor clearance depended on CD4⁺ and CD8⁺ T cells, but not NK cells. Additionally, 3p-RNA induced PD-L1 expression on HCC cells, enhancing their sensitivity to anti-PD-1 immune checkpoint therapy in vivo. RIG-I activation via 3p-RNA therapy shows promise as an immunotherapeutic strategy for hepatocellular carcinoma (HCC). Future investigations need to focus on tumor-intrinsic factors to understand heterogeneity between tumors and to overcome resistance mechanisms.

    Author Info: (1) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (2) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (3) LMU Klinikum Munich Germany. ROR: https://ror.or

    Author Info: (1) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (2) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (3) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (4) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (5) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (6) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (7) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (8) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (9) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (10) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (11) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (12) Ludwig-Maximilians-UniversitŠt MŸnchen Munich, Bavaria Germany. ROR: https://ror.org/05591te55 (13) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (14) Sanofi (Germany) Frankfurt Germany. ROR: https://ror.org/03ytdtb31 (15) Sanofi (Germany) Frankfurt Germany. ROR: https://ror.org/03ytdtb31 (16) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (17) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (18) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (19) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32 (20) LMU Klinikum Munich Germany. ROR: https://ror.org/02jet3w32

    Citation: Mol Cancer Ther 2026 Jun 25 Epub06/25/2026

    Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42345470

    Tags:
    Close Modal

    Subscribe to our mailing list

    GDPR Marketing Permissions

    The Fritsch Foundation/ACIR.org will use the information you provide on this form to be in touch with you and to send you a weekly digest on cance immunotherapy. Click below to confirm that you want to receive the weekly digest by:

    You can change your mind at any time by clicking the unsubscribe link in the footer of any email you receive from us, or by contacting us at contact@acir.org. We will treat your information with respect and will never share it with any third-parties. By clicking below, you agree that we may process your information in accordance with these terms.

    We use Mailchimp as our marketing platform. By clicking below to subscribe, you acknowledge that your information will be transferred to Mailchimp for processing. Learn more about Mailchimp's privacy practices here.

    Close Modal

    Small change for you. Big change for us!

    This Thanksgiving season, show your support for cancer research by donating your change.

    In less than a minute, link your credit card with our partner RoundUp App.

    Every purchase you make with that card will be rounded up and the change will be donated to ACIR.

    All transactions are securely made through Stripe.