Tryptophan degradation by intestinal Bacteroides induces anti-tumor immunity and limits melanoma growth
(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
In vivo engineering tumor cells to a universal "all-in-one" cancer vaccine with full antigen spectrum
(1) Wang W (2) Huang Y (3) Zhang J (4) Wang Y (5) Yu Z (6) Zhang F (7) Zhang H (8) Zhang R (9) Zhong R (10) Zhong H (11) Zhang L (12) Liu C (13) Shen C (14) Li Z (15) Wang M (16) Yang X
(1) Wang W (2) Huang Y (3) Zhang J (4) Wang Y (5) Yu Z (6) Zhang F (7) Zhang H (8) Zhang R (9) Zhong R (10) Zhong H (11) Zhang L (12) Liu C (13) Shen C (14) Li Z (15) Wang M (16) Yang X
Author Info: (1) Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. (2) Sheng Yushou Center of Cell B

Author Info: (1) Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. (2) Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. (3) Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. (4) Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. (5) Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. (6) Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. (7) Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. (8) Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. (9) Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. (10) Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. (11) Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (12) Cellular and Molecular Medicine, School of life sciences, University of Bristol, Bristol, UK. (13) Department of mathematics and statistics, Northeastern University at Qinhuangdao, Qinhuangdao, China. (14) Department of Biomedical Sciences, University College London, London, UK. (15) Department of Gynaecology and Obstetrics, Shanghai Pudong New Area People's Hospital, Shanghai, China. (16) Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Department of Gynaecology and Obstetrics, Shanghai Pudong New Area People's Hospital, Shanghai, China. Engineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai, China.

Citation: Sci Adv 2026 Jul 10 12:eaee5201 Epub07/08/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42418568
The efficacy of immunotherapy in glioma requires distal B cell responses in tumor-draining lymph nodes
(1) Kim Y (2) Kang I (3) Kang BH (4) Park WH (5) Kim CW (6) Kim HJ (7) La J (8) Kwon MS (9) Park SH (10) Im SH (11) Kim HC (12) Ku KB (13) Kim M (14) Oh JE (15) Lee HK
(1) Kim Y (2) Kang I (3) Kang BH (4) Park WH (5) Kim CW (6) Kim HJ (7) La J (8) Kwon MS (9) Park SH (10) Im SH (11) Kim HC (12) Ku KB (13) Kim M (14) Oh JE (15) Lee HK
Author Info: (1) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (2) Laboratory of Host D

Author Info: (1) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (2) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (3) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (4) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (5) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (6) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (7) Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (8) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (9) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (10) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (11) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (12) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Department of Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea. (13) Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (14) Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. (15) Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Regenerative Medical Research Institute (reMRI) for Aging-Related Diseases, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.

Citation: Sci Immunol 2026 Jul 10 11:eadz2494 Epub07/10/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42430444
mRNA lipid nanoparticle cancer vaccine platform delivering multiple STING activators for enhanced antitumor activity
(1) Zeng Y (2) Xu J (3) Wang J (4) Xue L (5) Liu J (6) Geisler HC (7) Ma X (8) Melamed JR (9) Shi Q (10) Padilla MS (11) Luo Z (12) Zhu J (13) Thatte AS (14) Figueroa-Espada CG (15) Ang MJY (16) Murray AM (17) Yamagata HM (18) Kim D (19) Metzloff AE (20) Weissman D (21) Mitchell MJ
(1) Zeng Y (2) Xu J (3) Wang J (4) Xue L (5) Liu J (6) Geisler HC (7) Ma X (8) Melamed JR (9) Shi Q (10) Padilla MS (11) Luo Z (12) Zhu J (13) Thatte AS (14) Figueroa-Espada CG (15) Ang MJY (16) Murray AM (17) Yamagata HM (18) Kim D (19) Metzloff AE (20) Weissman D (21) Mitchell MJ
Author Info: (1) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (2) Department of Bioengineering, University of Pennsylvania, P

Author Info: (1) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (2) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (3) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (4) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (5) Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (6) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (7) Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100190, China. ROR: https://ror.org/04f49ff35 (8) Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (9) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (10) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (11) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (12) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (13) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (14) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (15) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Republic of Singapore, Singapore 138668, Singapore. ROR: https://ror.org/036wvzt09 (16) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (17) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (18) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (19) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (20) Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 (21) Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 Penn Institute for RNA Innovation, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10 Center for Precision Engineering for Health, University of Pennsylvania, Philadelphia, PA 19104. ROR: https://ror.org/00b30xv10

Citation: Proc Natl Acad Sci U S A 2026 Jul 14 123:e2525718123 Epub07/08/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42418483
Epigenetic landscape, key transcriptional regulators, and in vivo identification of human Tr1 cells
(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) Mller F (14) Greenleaf WJ (15) Chang HY (16) Roncarolo MG
(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) Mller F (14) Greenleaf WJ (15) Chang HY (16) Roncarolo MG
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, Saarbrcken, 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
The CARM1 epigenetic enzyme inhibits cross-presenting dendritic cell function in cancer immunity
(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
(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
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
Generalizable AI predicts immunotherapy outcomes across cancers and treatments
(1) Shen W (2) Moon I (3) Nguyen TH (4) Li MM (5) Huang Y (6) Nair N (7) Marbach D (8) Zitnik M
(1) Shen W (2) Moon I (3) Nguyen TH (4) Li MM (5) Huang Y (6) Nair N (7) Marbach D (8) Zitnik M
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
Enhancement of ferroptosis in escape variant tumor cells by IFN-γ derived from antigen-specific T cells controls tumor with heterogeneity
Spotlight(1) Ehara D (2) Yasui K (3) Yoneda M (4) Muraoka D (5) Deng S (6) Miao P (7) Jiang C (8) Sun H (9) Okamoto S (10) Amaishi Y (11) Murota H (12) Ikeda H
To enhance immunotherapy efficacy against escape variant clones, Ehara et al. combined MART-1 TCR-T cells with the ferroptosis inducer RSL3. IFNγ secreted by the TCR-T cells enhanced the susceptibility of melanoma cells to ferroptosis. In mice injected with an equal mix of 526MEL and β2mKO cells, the combination treatment inhibited tumor growth, including reduction of the HLA-negative tumor mass, and significantly increased T cell infiltration compared to controls. In patients with melanoma, high expression of IFNγ signature genes STAT1 and IRF1 and low expression of SLC2A2 (counteracting ferroptosis) predicted better outcomes.
Contributed by Ute Burkhardt
(1) Ehara D (2) Yasui K (3) Yoneda M (4) Muraoka D (5) Deng S (6) Miao P (7) Jiang C (8) Sun H (9) Okamoto S (10) Amaishi Y (11) Murota H (12) Ikeda H
To enhance immunotherapy efficacy against escape variant clones, Ehara et al. combined MART-1 TCR-T cells with the ferroptosis inducer RSL3. IFNγ secreted by the TCR-T cells enhanced the susceptibility of melanoma cells to ferroptosis. In mice injected with an equal mix of 526MEL and β2mKO cells, the combination treatment inhibited tumor growth, including reduction of the HLA-negative tumor mass, and significantly increased T cell infiltration compared to controls. In patients with melanoma, high expression of IFNγ signature genes STAT1 and IRF1 and low expression of SLC2A2 (counteracting ferroptosis) predicted better outcomes.
Contributed by Ute Burkhardt
ABSTRACT: Tumor masses often exhibit heterogeneity, including escape variant clones that lack antigen-presenting machinery and/or tumor antigens, which poses a major challenge to immunotherapy. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has been shown to effectively induce cell death in various tumor cells. Recent studies have reported that IFN-γ suppresses the expression of System Xc-, thereby enhancing the induction of ferroptosis. Based on this, we hypothesized that combining immunotherapy with ferroptosis inducers could enhance antitumor effects against both antigen-positive and antigen-negative tumor cells. We found that combining RSL3, a ferroptosis inducer, with MART-1-specific TCR-T cells eradicates a heterogeneous tumor model consisting of human melanoma cells and their β2 microglobulin knockout counterparts. In NOG mice, this combination therapy demonstrates a significant antitumor effect against tumors with heterogeneity. These findings suggest that integrating ferroptosis inducers with immunotherapy could overcome the limitations imposed by escape variant tumor clones, offering a promising strategy for cancer treatment.
Author Info: (1) Nagasaki University Nagasaki Japan. ROR: https://ror.org/058h74p94 (2) Nagasaki University Nagasaki Japan. ROR: https://ror.org/058h74p94 (3) Nagasaki University Nagasaki Japan

Author Info: (1) Nagasaki University Nagasaki Japan. ROR: https://ror.org/058h74p94 (2) Nagasaki University Nagasaki Japan. ROR: https://ror.org/058h74p94 (3) Nagasaki University Nagasaki Japan. ROR: https://ror.org/058h74p94 (4) Aichi Cancer Center Research Institute Chikusa-ku, Nagoya, Aichi Japan. (5) Nagasaki University Nagasaki Japan. ROR: https://ror.org/058h74p94 (6) Nagasaki University Nagasaki Japan. ROR: https://ror.org/058h74p94 (7) Nagasaki University Nagasaki Japan. ROR: https://ror.org/058h74p94 (8) Nagasaki University Nagasaki Japan. ROR: https://ror.org/058h74p94 (9) Takara Bio Inc. Kusatsu, Shiga Japan. (10) Takara Bio Inc. Otsu, Shiga Japan. (11) Nagasaki University Nagasaki Japan. ROR: https://ror.org/058h74p94 (12) Nagasaki University Nagasaki, Nagasaki Japan. ROR: https://ror.org/058h74p94

Citation: Cancer Immunol Res 2026 Jul 3 Epub07/03/2026
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/42397036
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
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
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
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
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
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
