SYS6010, epidermal growth factor receptor-targeting antibody-drug conjugate for advanced non-small cell lung cancer: A phase 1 trial
(1) Li ZM (2) Zhou Z (3) He ZY (4) Han L (5) Fang J (6) Sun HM (7) Liu HF (8) Wang MX (9) Liu YB (10) Qu XJ (11) Yao Y (12) Gong Y (13) Yu Y (14) Shi HQ (15) Wang Y (16) Su CX (17) Yang KY (18) Shang YH (19) Ruan J (20) Yuan XL (21) Zhang MJ (22) Luo H (23) Cui JW (24) Lin XY (25) Li MX (26) Lou HZ (27) Yang RX (28) Wu H (29) Wang XC (30) Dan M (31) Zhang LQ (32) Su YZ (33) Wan XC (34) Zou K (35) Yang YY (36) Lu S
UV irradiation drives lineage-specific MITF-mediated transcription of PD-L1 to confer immune tolerance to UV-mutated melanocytes
(1) Lo JA (2) Rachmin I (3) Flesher JL (4) Wu X (5) Kawakami A (6) Hejna M (7) Boozer JR (8) Nguyen N (9) King AD (10) Ji Y (11) Germana S (12) Kemeny LV (13) van der Sande AAJ (14) Cheng JB (15) Lotem M (16) Utne TR (17) Zhan Y (18) Roider EM (19) Mujahid N (20) Byrne EH (21) Singh S (22) Saidani M (23) Martineau S (24) Holic N (25) Baldeschi C (26) Martinat C (27) Freeman GJ (28) Hacohen N (29) Flaherty KT (30) Boland GM (31) Song JS (32) Sharpe AH (33) Demehri S (34) Yee C (35) Allouche J (36) Fisher DE
(1) Lo JA (2) Rachmin I (3) Flesher JL (4) Wu X (5) Kawakami A (6) Hejna M (7) Boozer JR (8) Nguyen N (9) King AD (10) Ji Y (11) Germana S (12) Kemeny LV (13) van der Sande AAJ (14) Cheng JB (15) Lotem M (16) Utne TR (17) Zhan Y (18) Roider EM (19) Mujahid N (20) Byrne EH (21) Singh S (22) Saidani M (23) Martineau S (24) Holic N (25) Baldeschi C (26) Martinat C (27) Freeman GJ (28) Hacohen N (29) Flaherty KT (30) Boland GM (31) Song JS (32) Sharpe AH (33) Demehri S (34) Yee C (35) Allouche J (36) Fisher DE
Author Info: (1) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Department of Dermatology, Beth

Author Info: (1) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Department of Dermatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. (2) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (3) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (4) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (5) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Department of Dermatology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan. (6) Department of Physics, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA. (7) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (8) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (9) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (10) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Department of Stomatology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong, China. (11) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (12) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; HCEMM-SU Translational Dermatology Research Group, Semmelweis University, Budapest 1085, Hungary; Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest 1094, Hungary; Department of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, Budapest 1085, Hungary; MTA-SE Lendlet "Momentum" Dermatology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest 1085, Hungary. (13) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (14) Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA; Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA 94121, USA. (15) Lautenberg Center for Immunology and Cancer Research, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel; Center for Melanoma and Cancer Immunotherapy, Sharett Institute of Oncology, Jerusalem 91120, Israel; Hadassah Cancer Research Institute, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel. (16) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (17) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (18) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Department of Dermatology, University Hospital of Basel, 4031 Basel, Switzerland. (19) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Department of Dermatology, University of Utah, Salt Lake City, UT 84132, USA. (20) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (21) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. (22) IStem, CECS, Corbeil-Essonnes 91100, France. (23) Universit Paris-Saclay, Universit d'Evry, Inserm, IStem, UMR861, Corbeil-Essonnes 91100, France. (24) Universit Paris-Saclay, Universit d'Evry, Inserm, IStem, UMR861, Corbeil-Essonnes 91100, France. (25) Universit Paris-Saclay, Universit d'Evry, Inserm, IStem, UMR861, Corbeil-Essonnes 91100, France. (26) Universit Paris-Saclay, Universit d'Evry, Inserm, IStem, UMR861, Corbeil-Essonnes 91100, France. (27) Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA. (28) Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02142, USA. (29) Mass General Brigham Cancer Institute, Boston, MA 02114, USA. (30) Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA. (31) Department of Physics, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA. (32) Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA. (33) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. (34) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Parker Institute of Cancer Immunotherapy, San Francisco, CA 94129, USA. (35) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Universit Paris-Saclay, Universit d'Evry, Inserm, IStem, UMR861, Corbeil-Essonnes 91100, France. Electronic address: jeallouche@gmail.com. (36) Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. Electronic address: dfisher3@mgh.harvard.edu.

Citation: Immunity 2026 Aug 13 Epub08/13/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42594873
Coordinated immune activation following KRAS inhibition in syngeneic models reveals molecular pathways that potentiate and limit antitumor immunity
(1) Lu DR (2) Osgood T (3) Ma S (4) Zhang H (5) Kanke M (6) Tan JA (7) Paudel SN (8) Zhou H (9) Estrada J (10) Yamawaki T (11) Tarbell K (12) Rex K (13) DeVoss J (14) Martin S (15) Wang S (16) Canon J (17) Lipford JR (18) Coxon A (19) Li CM
(1) Lu DR (2) Osgood T (3) Ma S (4) Zhang H (5) Kanke M (6) Tan JA (7) Paudel SN (8) Zhou H (9) Estrada J (10) Yamawaki T (11) Tarbell K (12) Rex K (13) DeVoss J (14) Martin S (15) Wang S (16) Canon J (17) Lipford JR (18) Coxon A (19) Li CM
Author Info: (1) Amgen Inc. South San Francisco, CA United States. (2) Amgen Inc. Thousand Oaks, CA United States. (3) Amgen Inc. South San Francisco, CA United States. (4) Amgen Inc. South San

Author Info: (1) Amgen Inc. South San Francisco, CA United States. (2) Amgen Inc. Thousand Oaks, CA United States. (3) Amgen Inc. South San Francisco, CA United States. (4) Amgen Inc. South San Francisco, CA United States. (5) Amgen (United States) South San Franciso United States. ROR: https://ror.org/03g03ge92 (6) Amgen (United States) South San Francisco, CA United States. ROR: https://ror.org/03g03ge92 (7) Amgen Inc. Thousand Oaks, CA United States. (8) Amgen (United States) South San Francisco, CA United States. ROR: https://ror.org/03g03ge92 (9) Amgen Inc. Thousand Oaks, CA United States. (10) Amgen Inc. South San Francisco, CA United States. (11) Amgen Inc. South San Francisco, CA United States. (12) Amgen Inc. Thousand Oaks, CA United States. (13) Amgen (United States) South San Francisco, CA United States. ROR: https://ror.org/03g03ge92 (14) Amgen Inc. South San Francisco, CA United States. (15) Amgen Inc. South San Francisco, CA United States. (16) Amgen Inc. Thousand Oaks, CA United States. (17) Amgen (United States) United States. ROR: https://ror.org/03g03ge92 (18) Amgen Inc. Thousand Oaks, CA United States. (19) Amgen (United States) South San Francisco, CA United States. ROR: https://ror.org/03g03ge92

Citation: Cancer Immunol Res 2026 Jul 3 Epub07/03/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42397029
CAR T Cells Targeting O-Glycosylated Fibronectin Exhibit Potent Cytolytic Activity and Combine with Tumoral Toll-Like Receptor Agonism to Overcome Tumor Resistance
(1) King-Peoples TR (2) Keane JT (3) Lewis HS (4) Liu F (5) Brookens SK (6) Dagher OK (7) Parvathaneni K (8) Gardner BL (9) Ahmed A (10) Furth EE (11) Lal P (12) Posey AD
(1) King-Peoples TR (2) Keane JT (3) Lewis HS (4) Liu F (5) Brookens SK (6) Dagher OK (7) Parvathaneni K (8) Gardner BL (9) Ahmed A (10) Furth EE (11) Lal P (12) Posey AD
Author Info: (1) University of Pennsylvania Philadelphia, PA United States. ROR: https://ror.org/00b30xv10 (2) University of Pennsylvania United States. ROR: https://ror.org/00b30xv10 (3) Unive

Author Info: (1) University of Pennsylvania Philadelphia, PA United States. ROR: https://ror.org/00b30xv10 (2) University of Pennsylvania United States. ROR: https://ror.org/00b30xv10 (3) University of Pennsylvania Philadelphia, Pennsylvania United States. ROR: https://ror.org/00b30xv10 (4) University of Pennsylvania Philadelphia, Pennsylvania United States. ROR: https://ror.org/00b30xv10 (5) University of Pennsylvania United States. ROR: https://ror.org/00b30xv10 (6) University of Pennsylvania United States. ROR: https://ror.org/00b30xv10 (7) University of Pennsylvania Philadelphia United States. ROR: https://ror.org/00b30xv10 (8) University of Pennsylvania United States. ROR: https://ror.org/00b30xv10 (9) University of Pennsylvania United States. ROR: https://ror.org/00b30xv10 (10) University of Pennsylvania Philadelphia, PA United States. ROR: https://ror.org/00b30xv10 (11) Hospital of the University of Pennsylvania Philadelphia, PA United States. ROR: https://ror.org/02917wp91 (12) University of Pennsylvania Philadelphia, PA United States. ROR: https://ror.org/00b30xv10

Citation: Cancer Immunol Res 2026 Jul 3 Epub07/03/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42397032
Peripheral Th17 immune signature associates with excellent response to anti-PD1/anti-PD-L1 therapy across solid tumors
(1) Li HL (2) Charmsaz S (3) Kao C (4) Pazzi C (5) Brancati M (6) Leatherman JM (7) Zhao LX (8) Arif W (9) Lee RP (10) Hernandez J (11) Gross NE (12) Ellis C (13) Thoburn C (14) Ged Y (15) Hoffman-Censits J (16) Lipson EJ (17) Baretti M (18) Chandler GS (19) Mohindra R (20) Tang L (21) Bansal S (22) Guha A (23) Jaffee EM (24) Zabransky DJ (25) Ho WJ (26) Yarchoan M (27) Nakazawa M
(1) Li HL (2) Charmsaz S (3) Kao C (4) Pazzi C (5) Brancati M (6) Leatherman JM (7) Zhao LX (8) Arif W (9) Lee RP (10) Hernandez J (11) Gross NE (12) Ellis C (13) Thoburn C (14) Ged Y (15) Hoffman-Censits J (16) Lipson EJ (17) Baretti M (18) Chandler GS (19) Mohindra R (20) Tang L (21) Bansal S (22) Guha A (23) Jaffee EM (24) Zabransky DJ (25) Ho WJ (26) Yarchoan M (27) Nakazawa M
Author Info: (1) Sidney Kimmel Comprehensive Cancer Center Baltimore, MD United States. (2) Johns Hopkins Medicine Baltimore, MD United States. (3) Johns Hopkins Medicine Baltimore, MD United S

Author Info: (1) Sidney Kimmel Comprehensive Cancer Center Baltimore, MD United States. (2) Johns Hopkins Medicine Baltimore, MD United States. (3) Johns Hopkins Medicine Baltimore, MD United States. (4) Sidney Kimmel Comprehensive Cancer Center United States. (5) Johns Hopkins Medicine Baltimore, MD United States. (6) Sidney Kimmel Comprehensive Cancer Center Baltimore, MD United States. (7) Sidney Kimmel Comprehensive Cancer Center United States. (8) Johns Hopkins University United States. (9) Johns Hopkins Medicine Baltimore, MD United States. (10) Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore, MD United States. (11) Johns Hopkins Medicine Baltimore, Maryland United States. (12) Sidney Kimmel Comprehensive Cancer Center United States. (13) Johns Hopkins Medicine Baltimore, MD United States. (14) Johns Hopkins Medicine Baltimore United States. (15) Johns Hopkins Medicine Baltimore, MD United States. (16) Johns Hopkins Medicine BALTIMORE, MD United States. (17) Johns Hopkins Medicine Baltimore, MD United States. (18) Roche (Switzerland) Basel Switzerland. (19) Roche (Switzerland) Basel Switzerland. (20) Genentech South San Francisco, CA United States. (21) Genentech San Francisco, CA United States. (22) Genentech San Francisco, CA United States. (23) Johns Hopkins University Baltimore, MD United States. (24) Johns Hopkins Medicine Baltimore, MD United States. (25) Johns Hopkins University Baltimore, MD United States. (26) Johns Hopkins Medicine Baltimore, MD United States. (27) Johns Hopkins Medicine Baltimore, MD United States.

Citation: Cancer Immunol Res 2026 Jun 26 Epub06/26/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42360819
Intracranial delivery of B7-H3-targeting CAR-T cells for recurrent glioblastoma: a phase 1 trial
(1) Zhang Y (2) Chi X (3) Feng R (4) Xian N (5) Huang N (6) Sun S (7) Zhao X (8) Zhang P (9) Liu K (10) Ma Y (11) Zhang Y (12) Zhang K (13) Wang S (14) Chen X (15) Zhang J (16) Huang W (17) Huang B (18) Su TT (19) Yeung J (20) He J (21) Chen L (22) Ji N (23) Huang G
(1) Zhang Y (2) Chi X (3) Feng R (4) Xian N (5) Huang N (6) Sun S (7) Zhao X (8) Zhang P (9) Liu K (10) Ma Y (11) Zhang Y (12) Zhang K (13) Wang S (14) Chen X (15) Zhang J (16) Huang W (17) Huang B (18) Su TT (19) Yeung J (20) He J (21) Chen L (22) Ji N (23) Huang G
Author Info: (1) Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. (2) Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical Univ

Author Info: (1) Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. (2) Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. (3) Tcelltech Biological Science and Technology, Fuzhou, China. (4) Tcelltech Biological Science and Technology, Fuzhou, China. Institute of Immunotherapy, Fujian Medical University, Fuzhou, China. (5) Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. (6) Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Department of Neuroradiology, Beijing Neurosurgical Institute, Beijing, China. (7) Department of Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. (8) Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. (9) Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. (10) Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. (11) Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. (12) Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. (13) Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. (14) Tcelltech Biological Science and Technology, Fuzhou, China. (15) Tcelltech Biological Science and Technology, Fuzhou, China. (16) Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China. (17) Department of Immunobiology and Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, USA. (18) Department of Immunobiology and Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, USA. (19) Department of Immunobiology and Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, USA. Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA. (20) Department of Immunobiology and Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, USA. (21) Department of Immunobiology and Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, USA. lieping.chen@yale.edu. (22) Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. jinan@mail.ccmu.edu.cn. (23) Tcelltech Biological Science and Technology, Fuzhou, China. ghuang@tcelltech.com. Institute of Immunotherapy, Fujian Medical University, Fuzhou, China. ghuang@tcelltech.com.

Citation: Nat Med 2026 Aug 6 Epub08/06/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42562965
Tags:
Fc-optimized GITR antibody enhances a CD4 T cell-dendritic cell crosstalk to promote antitumor immunity
(1) Avraham Y (2) Barth N (3) Yair Bar-On T (4) Toval B (5) Habshush Menachem A (6) Blanga J (7) Herzog E (8) Rotem H (9) Shapir Itai Y (10) Feferman T (11) Biton M (12) Dahan R
(1) Avraham Y (2) Barth N (3) Yair Bar-On T (4) Toval B (5) Habshush Menachem A (6) Blanga J (7) Herzog E (8) Rotem H (9) Shapir Itai Y (10) Feferman T (11) Biton M (12) Dahan R
Author Info: (1) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. (2) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. (3) Depa

Author Info: (1) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. (2) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. (3) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. (4) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. (5) Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel. (6) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. (7) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. (8) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. (9) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. (10) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. (11) Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel. (12) Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. rony.dahan@weizmann.ac.il.

Citation: Nat Cancer 2026 Aug 5 Epub08/05/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42557403
Oncogenic Kras targeting with MRTX1133 or Daraxonrasib specifically synergize with anti-CTLA4 to promote anti-tumor immunity in pancreatic cancer
SpotlightKrishnan K. Mahadevan (1), Ana S. Maldonado (1), Bingrui Li (1), Aaron A. Bickert (1), Adrian Kacperczyk-Perdyan (1,2), Shreyasee V. Kumbhar (1), Sujan Piya (3), Amari M. Sockwell (1), Sami J. Morse (1), Kent Arian (1), Hikaru Sugimoto (1), Shabnam Shalapour (1), David S. Hong (4), Timothy P. Heffernan (5), Anirban Maitra (3)& Raghu Kalluri (1,6,7,8)
To overcome PDAC resistance to Kras* targeting using MRTX1133 or daraxonrasib, which enhances infiltration T cells, including various CD8+ T cell, CD4+ conventional T cell, and Treg phenotypes, Mahadevan et al. found that the addition of anti-CTLA-4 (but not other ICB) synergized by further increasing TILs, reprogramming Tregs to a more naive (less suppressive) phenotype, reversing exhaustion in CD8+ T cells, and promoting the formation of TLSs, together resulting in better PDAC suppression and longer survival. Treg reprogramming occurred through epigenetic downregulation of AP-1 transcription factors in the IL-10 and IL-35 promoter regions.
Contributed by Lauren Hitchings
Krishnan K. Mahadevan (1), Ana S. Maldonado (1), Bingrui Li (1), Aaron A. Bickert (1), Adrian Kacperczyk-Perdyan (1,2), Shreyasee V. Kumbhar (1), Sujan Piya (3), Amari M. Sockwell (1), Sami J. Morse (1), Kent Arian (1), Hikaru Sugimoto (1), Shabnam Shalapour (1), David S. Hong (4), Timothy P. Heffernan (5), Anirban Maitra (3)& Raghu Kalluri (1,6,7,8)
To overcome PDAC resistance to Kras* targeting using MRTX1133 or daraxonrasib, which enhances infiltration T cells, including various CD8+ T cell, CD4+ conventional T cell, and Treg phenotypes, Mahadevan et al. found that the addition of anti-CTLA-4 (but not other ICB) synergized by further increasing TILs, reprogramming Tregs to a more naive (less suppressive) phenotype, reversing exhaustion in CD8+ T cells, and promoting the formation of TLSs, together resulting in better PDAC suppression and longer survival. Treg reprogramming occurred through epigenetic downregulation of AP-1 transcription factors in the IL-10 and IL-35 promoter regions.
Contributed by Lauren Hitchings
ABSTRACT: Lack of sustained response to oncogenic Kras (Kras*) inhibition in pancreatic ductal adenocarcinoma (PDAC) underscores the need to identify effective combination therapies. Here, we demonstrate that Kras* targeting using MRTX1133 or Daraxonrasib recruits diverse T-cell infiltrates, including regulatory (Tregs), effector and exhausted T cells into the PDAC microenvironment. Kras* inhibition induces T-cell influx and offers a therapeutic window to specifically prime PDAC to anti-CTLA4 immune checkpoint blockade efficacy, in contrast to anti-PD1, anti-Tim3, anti-Lag3, anti-Vista, and anti-4-1BB agonist combination therapy. Mechanistically, anti-CTLA4 combination therapy transcriptionally reprograms effector Tregs to a naive phenotype, reverses CD8+ T-cell exhaustion, and promotes recruitment of functional tertiary lymphoid structures to mediate anti-tumor immunity. Single-cell ATAC sequencing reveals that Treg reprogramming by anti-CTLA4 is epigenetically regulated by downregulation of AP-1 family transcription factors in the IL-35 promoter region. This study reveals an actionable vulnerability in the adaptive immune response in Kras* targeted PDAC with immediate clinical implications.
Author Info: (1) Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA (2) 3P-Medicine Laboratory, Medical University of Gdansk, 80-210 Gdansk, Poland (3

Author Info: (1) Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA (2) 3P-Medicine Laboratory, Medical University of Gdansk, 80-210 Gdansk, Poland (3) Departments of Anatomical Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA (4) Department of Investigative Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA (5) Institute for Applied Science and TRACTION platform, University of Texas MD Anderson Cancer Center, Houston, TX, USA (6) Department of Bioengineering, Rice University, Houston, TX, USA (7) Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA (8) Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA

Citation: Nat com 2026
Tags:
The Dendritic Cell-based Vaccine PROTEXI leverages Antiviral CD4 T cell Memory to boost anti-tumor immune responses in mice Spotlight
(1) Kang JM (2) Han EH (3) Choi JK (4) Youm S (5) Pareek T (6) Levi L (7) Kim SJ (8) Letterio J (9) Lim S
Kang and Han et al. developed PROTEXI, a vaccine platform comprising autologous DCs loaded with both tumor-specific CD8+ T and SARS-CoV-2 Spike protein CD4+ TH cell epitopes. In mouse tumor models, PROTEXI required both CD4+ and CD8+ T cells for efficacy and immune memory induction, and in ICI-resistant models, synergized with anti-PD-1 by revitalizing TEX cells. PROTEXI plus Vactosertib, a TGFβR inhibitor, activated “cold” TIMEs by driving T cell recruitment, cytotoxicity, and epitope spreading. PROTEXI was also efficacious in humanized mouse tumor models, dependent on pre-existing human CD4+ T cells against SARS-CoV-2 Spike epitopes.
Contributed by Paula Hochman
(1) Kang JM (2) Han EH (3) Choi JK (4) Youm S (5) Pareek T (6) Levi L (7) Kim SJ (8) Letterio J (9) Lim S
Kang and Han et al. developed PROTEXI, a vaccine platform comprising autologous DCs loaded with both tumor-specific CD8+ T and SARS-CoV-2 Spike protein CD4+ TH cell epitopes. In mouse tumor models, PROTEXI required both CD4+ and CD8+ T cells for efficacy and immune memory induction, and in ICI-resistant models, synergized with anti-PD-1 by revitalizing TEX cells. PROTEXI plus Vactosertib, a TGFβR inhibitor, activated “cold” TIMEs by driving T cell recruitment, cytotoxicity, and epitope spreading. PROTEXI was also efficacious in humanized mouse tumor models, dependent on pre-existing human CD4+ T cells against SARS-CoV-2 Spike epitopes.
Contributed by Paula Hochman
ABSTRACT: The efficacy of dendritic cell (DC) cancer vaccines is linked to poor immunogenicity of tumor-associated antigens and failure to elicit robust MHC class II-restricted CD4⁺ T-cell responses. Here, we introduce PROTEXI, a DC vaccine platform that optimizes tumor immunity by co-presenting tumor-specific CD8⁺ T-cell epitopes alongside CD4⁺ T helper epitopes from the SARS-CoV-2 Spike protein, leveraging widespread anti-viral immunity. In preclinical mouse models of melanoma and breast cancer, PROTEXI significantly reduces tumor growth and improves survival by promoting robust T cell infiltration into immune-cold tumors, increasing cytotoxic T cell responses via epitope spreading, and activating genes linked to optimal DC, NK cell, and T cell function. Furthermore, PROTEXI elicits superior responses when combined with other immunotherapy agents in models of therapy-resistant tumors. Finally, in a humanized mouse model of melanoma, PROTEXI vaccine co-presenting CD4⁺ T-specific Spike epitopes with CD8⁺ T cell-restricted PRAME and MAGE-A3 antigens, significantly reduces tumor burden. Thus, these data underscore the potential of harnessing pre-existing viral-specific immunity to enhance the efficacy of DC vaccines in immune-cold tumors.
Author Info: (1) The Angie Fowler Adolescent & Young Adult Cancer Institute, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, OH, USA. Department of Pediatric Hematology &

Author Info: (1) The Angie Fowler Adolescent & Young Adult Cancer Institute, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, OH, USA. Department of Pediatric Hematology & Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. (2) Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA. (3) Celloram Inc., 11000 Cedar Avenue STE 100F #23, Cleveland, OH, USA. (4) Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA. (5) Celloram Inc., 11000 Cedar Avenue STE 100F #23, Cleveland, OH, USA. (6) Celloram Inc., 11000 Cedar Avenue STE 100F #23, Cleveland, OH, USA. (7) MedPacto Inc., 92, Myeongdal-ro, Seocho-gu, Seoul, Republic of Korea. (8) The Angie Fowler Adolescent & Young Adult Cancer Institute, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, OH, USA. John.Letterio@UHHospitals.org. Department of Pediatric Hematology & Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. John.Letterio@UHHospitals.org. Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA. John.Letterio@UHHospitals.org. The Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA. John.Letterio@UHHospitals.org. (9) The Angie Fowler Adolescent & Young Adult Cancer Institute, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, OH, USA. SeunghwanLim@Celloram.com. Celloram Inc., 11000 Cedar Avenue STE 100F #23, Cleveland, OH, USA. SeunghwanLim@Celloram.com.

Citation: Nat Commun 2026 Jul 27 17: Epub07/27/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42509244
Tumor-induced dendritic cell deregulation perturbs T cell proliferation and predicts clinical outcome in acute lymphoblastic leukemia Spotlight
(1) Kumar A (2) Hamane K (3) Duault C (4) Lima-Junior JR (5) Jung DH (6) Qin H (7) Salcido S (8) Huang M (9) Guo X (10) Taghi Khani A (11) Sanchez Ortiz A (12) Ghoda L (13) Marcucci G (14) Lacayo NJ (15) Sakamoto KM (16) Hurtz C (17) Carroll M (18) Tasian SK (19) Geng H (20) Ji L (21) Armenian S (22) Izraeli S (23) Wu X (24) Maecker HT (25) Swaminathan S
Kumar et al. characterized the transcriptome and proteome of the DC compartment in both pediatric and adult ALL, and demonstrated that DC maturation into functional lineages was disrupted. Proliferation, antigen presentation, and cytokine production were impaired across all residual DC subsets, except progenitor/DC4 fractions, leading to a semi-mature, potentially tolerogenic phenotype with defective T cell priming. MYC overexpression in malignant lymphoblasts partly drove the disruption of DC homeostasis. A stimulated DC transcriptional signature at ALL diagnosis correlated with favorable outcomes in B-ALL, but adverse outcomes in T-ALL.
Contributed by Shishir Pant
(1) Kumar A (2) Hamane K (3) Duault C (4) Lima-Junior JR (5) Jung DH (6) Qin H (7) Salcido S (8) Huang M (9) Guo X (10) Taghi Khani A (11) Sanchez Ortiz A (12) Ghoda L (13) Marcucci G (14) Lacayo NJ (15) Sakamoto KM (16) Hurtz C (17) Carroll M (18) Tasian SK (19) Geng H (20) Ji L (21) Armenian S (22) Izraeli S (23) Wu X (24) Maecker HT (25) Swaminathan S
Kumar et al. characterized the transcriptome and proteome of the DC compartment in both pediatric and adult ALL, and demonstrated that DC maturation into functional lineages was disrupted. Proliferation, antigen presentation, and cytokine production were impaired across all residual DC subsets, except progenitor/DC4 fractions, leading to a semi-mature, potentially tolerogenic phenotype with defective T cell priming. MYC overexpression in malignant lymphoblasts partly drove the disruption of DC homeostasis. A stimulated DC transcriptional signature at ALL diagnosis correlated with favorable outcomes in B-ALL, but adverse outcomes in T-ALL.
Contributed by Shishir Pant
ABSTRACT: Perturbations in dendritic cells (DCs) in B/T cell acute lymphoblastic leukemia (ALL), their cause(s) and consequence(s) on antileukemia immunity, and patient outcomes remain poorly explored. We find that maturation of DC1-6 subsets is disrupted in children and adults with ALL. Conventional DC1 and DC2 subpopulations are reduced at the expense of the progenitors and the DC4 fractions in ALL. The potential to mature, present antigens, and produce cytokines for initiating T cell surveillance appears to be impaired in every ALL DC subset. Such DC subsets are accordingly unable to induce T cell proliferation compared to DCs from healthy donors. MYC overexpression in ALL cells disrupts DC homeostasis and reduces the ability of DCs to induce T cell proliferation. Predominance of cells with transcriptional signatures typical of "stimulated DCs" predicts favorable clinical outcomes in B-ALL, while it is associated with unfavorable outcomes in T-ALL. Phenotyping DC subsets at ALL diagnosis could thus be valuable in informing treatment outcomes.
Author Info: (1) Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA. (2) Department of Systems Biology, Beckman Research Institute of City of Hop

Author Info: (1) Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA. (2) Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA. (3) The Human Immune Monitoring Center (HIMC), Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. (4) Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA. (5) Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA. (6) Department of Molecular and Cellular Biology, City of Hope National Medical Center, Duarte, CA 91010, USA. (7) The Hematopoietic Tissue Biorepository/Research Pathology Shared Resources, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA. (8) Department of Pediatrics (Hematology and Oncology), Stanford University School of Medicine, Stanford, CA 94305, USA. (9) Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA. (10) Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA. (11) Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA. (12) The Hematopoietic Tissue Biorepository/Research Pathology Shared Resources, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA. (13) The Hematopoietic Tissue Biorepository/Research Pathology Shared Resources, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA; The Department of Hematological Malignancies Translational Science, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA. (14) Department of Pediatrics (Hematology and Oncology), Stanford University School of Medicine, Stanford, CA 94305, USA. (15) Department of Pediatrics (Hematology and Oncology), Stanford University School of Medicine, Stanford, CA 94305, USA. (16) Department of Basic Science, Division of Cancer Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA. (17) Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. (18) Division of Oncology and Center for Childhood Cancer Research, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pediatrics and Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. (19) Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. (20) Department of Clinical Population and Public Health Sciences, University of Southern California, Los Angeles, CA 91016, USA. (21) Department of Pediatrics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA. (22) Schneider Children's Medical Center, Tel Aviv University, Felsenstein Research Institute, Tel Aviv, Israel. (23) Department of Molecular and Cellular Biology, City of Hope National Medical Center, Duarte, CA 91010, USA. (24) The Human Immune Monitoring Center (HIMC), Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. (25) Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Department of Pediatrics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA; Center for RNA Biology and Therapeutics, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA. Electronic address: sswaminathan@coh.org.

Citation: Cell Rep Med 2026 Jul 28 102945 Epub07/28/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42520804
