Mutant KRAS peptide targeted CAR-T cells engineered for cancer therapy
(1) Benton A (2) Liu J (3) Poussin MA (4) Lang Goldgewicht A (5) Udawela M (6) Bear AS (7) Wellhausen N (8) Carreno BM (9) Smith PM (10) Beasley MD (11) Kiefel BR (12) Powell DJ Jr
Preferential tumor targeting of HER2 by iPSC-derived CAR T cells engineered to overcome multiple barriers to solid tumor efficacy
(1) Hosking MP (2) Shirinbak S (3) Omilusik K (4) Chandra S (5) Kaneko MK (6) Gentile A (7) Yamamoto S (8) Shrestha B (9) Grant J (10) Boyett M (11) Cardenas D (12) Keegan H (13) Ibitokou S (14) Pavon C (15) Mizoguchi T (16) Ihara T (17) Nakayama D (18) Abujarour R (19) Lee TT (20) Clarke R (21) Goodridge J (22) Peralta E (23) Maeda T (24) Takagi J (25) Arimori T (26) Kato Y (27) Valamehr B
(1) Hosking MP (2) Shirinbak S (3) Omilusik K (4) Chandra S (5) Kaneko MK (6) Gentile A (7) Yamamoto S (8) Shrestha B (9) Grant J (10) Boyett M (11) Cardenas D (12) Keegan H (13) Ibitokou S (14) Pavon C (15) Mizoguchi T (16) Ihara T (17) Nakayama D (18) Abujarour R (19) Lee TT (20) Clarke R (21) Goodridge J (22) Peralta E (23) Maeda T (24) Takagi J (25) Arimori T (26) Kato Y (27) Valamehr B
Author Info: (1) Fate Therapeutics, Inc., San Diego, CA, USA. Electronic address: martin.hosking@fatetherapeutics.com. (2) Fate Therapeutics, Inc., San Diego, CA, USA. (3) Fate Therapeutics, In
Author Info: (1) Fate Therapeutics, Inc., San Diego, CA, USA. Electronic address: martin.hosking@fatetherapeutics.com. (2) Fate Therapeutics, Inc., San Diego, CA, USA. (3) Fate Therapeutics, Inc., San Diego, CA, USA. (4) Fate Therapeutics, Inc., San Diego, CA, USA. (5) Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan. (6) Fate Therapeutics, Inc., San Diego, CA, USA. (7) Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan. (8) Fate Therapeutics, Inc., San Diego, CA, USA. (9) Fate Therapeutics, Inc., San Diego, CA, USA. (10) Fate Therapeutics, Inc., San Diego, CA, USA. (11) Fate Therapeutics, Inc., San Diego, CA, USA. (12) Fate Therapeutics, Inc., San Diego, CA, USA. (13) Fate Therapeutics, Inc., San Diego, CA, USA. (14) Fate Therapeutics, Inc., San Diego, CA, USA. (15) Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan. (16) Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan. (17) Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan. (18) Fate Therapeutics, Inc., San Diego, CA, USA. (19) Fate Therapeutics, Inc., San Diego, CA, USA. (20) Fate Therapeutics, Inc., San Diego, CA, USA. (21) Fate Therapeutics, Inc., San Diego, CA, USA. (22) Fate Therapeutics, Inc., San Diego, CA, USA. (23) Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan. (24) Institute for Protein Research, Osaka University, 3-2, Yamadaoka, Suita 565-0871, Osaka, Japan. (25) Institute for Protein Research, Osaka University, 3-2, Yamadaoka, Suita 565-0871, Osaka, Japan. (26) Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan. (27) Fate Therapeutics, Inc., San Diego, CA, USA. Electronic address: bob.valamehr@fatetherapeutics.com.
Citation: Cell Stem Cell 2025 May 30 Epub05/30/2025
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/40472844
TEIPP-vaccination in checkpoint-resistant non-small cell lung cancer: a first-in-human phase I/II dose-escalation study
(1) Emmers M (2) Welters MJP (3) Dietz MV (4) Santegoets SJ (5) Boekesteijn S (6) Stolk A (7) Loof NM (8) Dumoulin DW (9) Geel AL (10) Steinbusch LC (11) Valentijn ARPM (12) Cohen D (13) de Miranda NFCC (14) Smit EF (15) Gelderblom H (16) van Hall T (17) Aerts JG (18) van der Burg SH
(1) Emmers M (2) Welters MJP (3) Dietz MV (4) Santegoets SJ (5) Boekesteijn S (6) Stolk A (7) Loof NM (8) Dumoulin DW (9) Geel AL (10) Steinbusch LC (11) Valentijn ARPM (12) Cohen D (13) de Miranda NFCC (14) Smit EF (15) Gelderblom H (16) van Hall T (17) Aerts JG (18) van der Burg SH
Author Info: (1) Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. (2) Department of Medical Oncology, Oncode Institute, Leiden University Medical
Author Info: (1) Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. (2) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands. (3) Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. (4) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands. (5) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands. (6) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands. (7) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands. (8) Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. (9) Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. (10) Department of Pulmonary Disease, Leiden University Medical Center, Leiden, The Netherlands. (11) Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. (12) Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. (13) Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. (14) Department of Pulmonary Disease, Leiden University Medical Center, Leiden, The Netherlands. (15) Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands. (16) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands. (17) Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. (18) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands. shvdburg@lumc.nl.
Citation: Nat Commun 2025 May 28 16:4958 Epub05/28/2025
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/40436854
INBRX-106: a hexavalent OX40 agonist that drives superior antitumor responses via optimized receptor clustering
(1) Holay N (2) Yadav R (3) Ahn SJ (4) Kasiewicz MJ (5) Polovina A (6) Rolig AS (7) Staebler T (8) Becklund B (9) Simons ND (10) Koguchi Y (11) Eckelman BP (12) de Durana YD (13) Redmond WL
(1) Holay N (2) Yadav R (3) Ahn SJ (4) Kasiewicz MJ (5) Polovina A (6) Rolig AS (7) Staebler T (8) Becklund B (9) Simons ND (10) Koguchi Y (11) Eckelman BP (12) de Durana YD (13) Redmond WL
Author Info: (1) Earle A Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA. (2) Earle A Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA
Author Info: (1) Earle A Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA. (2) Earle A Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA. Oregon Health and Science University, Portland, Oregon, USA. (3) Inhibrx Biosciences Inc, La Jolla, California, USA. (4) Earle A Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA. (5) Inhibrx Biosciences Inc, La Jolla, California, USA. (6) Earle A Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA. Oregon Health and Science University, Portland, Oregon, USA. (7) Inhibrx Biosciences Inc, La Jolla, California, USA. (8) Inhibrx Biosciences Inc, La Jolla, California, USA. (9) Earle A Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA. (10) Earle A Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA. The Ohio State University, Columbus, Ohio, USA. (11) Inhibrx Biosciences Inc, La Jolla, California, USA. (12) Inhibrx Biosciences Inc, La Jolla, California, USA william.redmond@providence.org yaiza@inhibrx.com. (13) Earle A Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA william.redmond@providence.org yaiza@inhibrx.com.
Citation: J Immunother Cancer 2025 May 21 13: Epub05/21/2025
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/40404202
Adoptively transferred macrophages for cancer immunotherapy
(1) Park KS (2) Gottlieb AP (3) Janes ME (4) Prakash S (5) Kapate N (6) Suja VC (7) Wang LL (8) Guerriero JL (9) Mitragotri S
(1) Park KS (2) Gottlieb AP (3) Janes ME (4) Prakash S (5) Kapate N (6) Suja VC (7) Wang LL (8) Guerriero JL (9) Mitragotri S
Author Info: (1) John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, Massachusetts, USA. Wyss Institute for Biologically Inspired Engineering, Boston, Massa
Author Info: (1) John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, Massachusetts, USA. Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA. (2) John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, Massachusetts, USA. Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA. (3) John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, Massachusetts, USA. Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. (4) John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, Massachusetts, USA. (5) John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, Massachusetts, USA. Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. (6) John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, Massachusetts, USA. Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA. (7) John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, Massachusetts, USA. Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. (8) Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA. Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, Massachusetts, USA. Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts, USA. (9) John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, Massachusetts, USA mitragotri@seas.harvard.edu. Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, USA.
Citation: J Immunother Cancer 2025 May 24 13: Epub05/24/2025
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/40413021
Blockade of CLEVER-1 restrains immune evasion and enhances anti-PD-1 immunotherapy in gastric cancer
(1) Yu K (2) Cao Y (3) Zhang Z (4) Wang L (5) Gu Y (6) Xu T (7) Zhang X (8) Guo X (9) Shen Z (10) Qin J
(1) Yu K (2) Cao Y (3) Zhang Z (4) Wang L (5) Gu Y (6) Xu T (7) Zhang X (8) Guo X (9) Shen Z (10) Qin J
Author Info: (1) Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China. Gastric Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. (2) Department
Author Info: (1) Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China. Gastric Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. (2) Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China. Gastric Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. (3) Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China. Gastric Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. (4) Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China. Gastric Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. (5) Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China. Gastric Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. (6) Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China. (7) Department of Pathology, Zhongshan Hospital Fudan University, Shanghai, China. (8) Department of Pathology, Zhongshan Hospital Fudan University, Shanghai, China. (9) Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China qin.jing@zs-hospital.sh.cn shen.zhenbin@zs-hospital.sh.cn. Gastric Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China. (10) Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China qin.jing@zs-hospital.sh.cn shen.zhenbin@zs-hospital.sh.cn. Gastric Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China.
Citation: J Immunother Cancer 2025 May 22 13: Epub05/22/2025
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/40404204
Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire
(1) Cheloni G (2) Karagkouni D (3) Pita-Juarez Y (4) Torres D (5) Kanata E (6) Liegel J (7) Avigan Z (8) Saldarriaga I (9) Chedid G (10) Rallis K (11) Miles B (12) Tiwari G (13) Kim J (14) Mattie M (15) Rosenblatt J (16) Vlachos IS (17) Avigan D
(1) Cheloni G (2) Karagkouni D (3) Pita-Juarez Y (4) Torres D (5) Kanata E (6) Liegel J (7) Avigan Z (8) Saldarriaga I (9) Chedid G (10) Rallis K (11) Miles B (12) Tiwari G (13) Kim J (14) Mattie M (15) Rosenblatt J (16) Vlachos IS (17) Avigan D
Author Info: (1) Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. Harvard Medical School, Bos
Author Info: (1) Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (2) Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. (3) Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. (4) Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. (5) Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA. (6) Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (7) Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. (8) Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (9) Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (10) Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (11) Kite, a Gilead Company, Santa Monica, CA, USA. (12) Kite, a Gilead Company, Santa Monica, CA, USA. (13) Kite, a Gilead Company, Santa Monica, CA, USA. (14) Kite, a Gilead Company, Santa Monica, CA, USA. (15) Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (16) Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. Spatial Technologies Unit, Harvard Medical School Initiative for RNA Medicine, Boston, MA, USA. (17) Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. davigan@bidmc.harvard.edu. Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. davigan@bidmc.harvard.edu. Harvard Medical School, Boston, MA, USA. davigan@bidmc.harvard.edu.
Citation: Nat Commun 2025 May 23 16:4819 Epub05/23/2025
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/40410132
Fc-optimized anti-CTLA-4 antibodies increase tumor-associated high endothelial venules and sensitize refractory tumors to PD-1 blockade
SpotlightLucas Blanchard (1,2,5,*); Estefania Vina (1,2,5); Jerko Ljubetic (1,2); Cécile Meneur (1,2); Dorian Tarroux (1,2); Maria Baez (3); Alessandra Marino (3); Nathalie Ortega (1,2); David A. Knorr (3,4); Jeffrey V. Ravetch (3); and Jean-Philippe Girard (1,2,6,*)
Blanchard and Vina et al. investigated mechanisms by which anti-CTLA-4 mAbs modulate tumor-associated high endothelial venules (TA-HEVs), which are important for supporting lymphocyte entry into tumors. In mouse models, anti-CTLA-4 Fc-derived effector function was required to increase TA-HEVs. CD4+ T cells and IFNγ were also found to be important during anti-CTLA-4 therapy. Consequently, Fc engineering of ipilimumab was necessary to increase TA-HEVs in humanized mice. Combination with anti-PD-1 increased TA-HEVs, promoted CD4+ and CD8+ T cell infiltration into tumors, and sensitized cold, refractory tumors to PD-1 blockade.
Contributed by Katherine Turner
Lucas Blanchard (1,2,5,*); Estefania Vina (1,2,5); Jerko Ljubetic (1,2); Cécile Meneur (1,2); Dorian Tarroux (1,2); Maria Baez (3); Alessandra Marino (3); Nathalie Ortega (1,2); David A. Knorr (3,4); Jeffrey V. Ravetch (3); and Jean-Philippe Girard (1,2,6,*)
Blanchard and Vina et al. investigated mechanisms by which anti-CTLA-4 mAbs modulate tumor-associated high endothelial venules (TA-HEVs), which are important for supporting lymphocyte entry into tumors. In mouse models, anti-CTLA-4 Fc-derived effector function was required to increase TA-HEVs. CD4+ T cells and IFNγ were also found to be important during anti-CTLA-4 therapy. Consequently, Fc engineering of ipilimumab was necessary to increase TA-HEVs in humanized mice. Combination with anti-PD-1 increased TA-HEVs, promoted CD4+ and CD8+ T cell infiltration into tumors, and sensitized cold, refractory tumors to PD-1 blockade.
Contributed by Katherine Turner
ABSTRACT: The lack of T cells in tumors is a major hurdle to successful immune checkpoint therapy (ICT). Therefore, therapeutic strategies promoting T cell recruitment into tumors are warranted to improve the treatment efficacy. Here, we report that Fc-optimized anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies are potent re-modelers of tumor vasculature that increase tumor-associated high endothelial venules (TA-HEVs), specialized blood vessels supporting lymphocyte entry into tumors. Mechanistically, this effect is dependent on the Fc domain of anti-CTLA-4 antibodies and CD4+ T cells and involves interferon gamma (IFNγ). Unexpectedly, we find that the human anti-CTLA-4 antibody ipilimumab fails to increase TA-HEVs in a humanized mouse model. However, increasing its Fc effector function rescues the modulation of TA-HEVs, promotes CD4+ and CD8+ T cell infiltration into tumors, and sensitizes recalcitrant tumors to programmed cell death protein 1 (PD-1) blockade. Our findings suggest that Fc-optimized anti-CTLA-4 antibodies could be used to reprogram tumor vasculature in poorly immunogenic cold tumors and improve the efficacy of ICT.
Author Info: 1-Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
2-Equipe Labellisée LIGUE 2023, Paris, France
3-Laboratory of Mo
Author Info: 1-Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
2-Equipe Labellisée LIGUE 2023, Paris, France
3-Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY, USA
4-Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
5-These authors contributed equally
6-Lead contact
*Correspondence: lblanchard@rockefeller.edu, jean-philippe.girard@ipbs.fr
Citation: Cell rep med 2025
Immunopeptidomics-guided discovery and characterization of neoantigens for personalized cancer immunotherapy Spotlight
(1) Cai Y (2) Gong M (3) Zeng M (4) Leng F (5) Lv D (6) Guo J (7) Wang H (8) Li Y (9) Lin Q (10) Jing J (11) Zhang Y (12) Xu J (13) Li Y
To identify novel neoantigens, Cai et al. assembled an immunopeptidomics atlas from published tumor and normal tissue datasets. Non-canonical (non-coding; 15%) and canonical (85%) peptides exhibited similar tissue distribution and presentation. Tumor-derived peptides exhibited differential features compared to normal tissue-derived peptides, such as positively charged residues and basic AA anchors. Cancer- and tissue-specific machine learning models identified 2,523 immunogenic tumor-specific peptides (41% noncanonical), most of which were patient-specific. Three highly ranked candidate pan-cancer peptides induced proliferation and antitumor cytotoxic activity in T cells.
Contributed by Morgan Janes
(1) Cai Y (2) Gong M (3) Zeng M (4) Leng F (5) Lv D (6) Guo J (7) Wang H (8) Li Y (9) Lin Q (10) Jing J (11) Zhang Y (12) Xu J (13) Li Y
To identify novel neoantigens, Cai et al. assembled an immunopeptidomics atlas from published tumor and normal tissue datasets. Non-canonical (non-coding; 15%) and canonical (85%) peptides exhibited similar tissue distribution and presentation. Tumor-derived peptides exhibited differential features compared to normal tissue-derived peptides, such as positively charged residues and basic AA anchors. Cancer- and tissue-specific machine learning models identified 2,523 immunogenic tumor-specific peptides (41% noncanonical), most of which were patient-specific. Three highly ranked candidate pan-cancer peptides induced proliferation and antitumor cytotoxic activity in T cells.
Contributed by Morgan Janes
ABSTRACT: Neoantigens have emerged as ideal targets for personalized cancer immunotherapy. We depict the pan-cancer peptide atlas by comprehensively collecting immunopeptidomics from 531 samples across 14 cancer and 29 normal tissues, and identify 389,165 canonical and 70,270 noncanonical peptides. We reveal that noncanonical peptides exhibit comparable presentation levels as canonical peptides across cancer types. Tumor-specific peptides exhibit significantly distinct biochemical characteristics compared with those observed in normal tissues. We further propose an immunopeptidomic-guided machine learning-based neoantigen screening pipeline (MaNeo) to prioritize neo-peptides as immunotherapy targets. Benchmark analysis reveals MaNeo results in the accurate identification of shared and tumor-specific canonical and noncanonical neo-peptides. Last, we use MaNeo to detect and validate three neo-peptides in cancer cell lines, which can effectively induce increased proliferation of active T cells and T cell responses to kill cancer cells but not damage healthy cells. The pan-cancer peptide atlas and proposed MaNeo pipeline hold great promise for the discovery of canonical and noncanonical neoantigens for cancer immunotherapies.
Author Info: (1) State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China. (2) De
Author Info: (1) State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China. (2) Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, PR China. (3) State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China. (4) State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China. (5) State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China. (6) State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), School of Interdisciplinary Medicine and Engineering, Harbin Medical University, Harbin, Heilongjiang 150081, China. (7) Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, PR China. (8) The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China. (9) Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150040, China. (10) Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150040, China. (11) Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, PR China. (12) State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China. (13) State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), School of Interdisciplinary Medicine and Engineering, Harbin Medical University, Harbin, Heilongjiang 150081, China. Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150040, China.
Citation: Sci Adv 2025 May 23 11:eadv6445 Epub05/21/2025
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/40397742
Tags:
Mature tertiary lymphoid structures evoke intra-tumoral T and B cell responses via progenitor exhausted CD4+ T cells in head and neck cancer
Spotlight(1) Li H (2) Zhang MJ (3) Zhang B (4) Lin WP (5) Li SJ (6) Xiong D (7) Wang Q (8) Wang WD (9) Yang QC (10) Huang CF (11) Deng WW (12) Sun ZJ
Li and Zhang et al. reported the presence of stem-like T cells and B cells at various stages of tertiary lymphoid structure (TLS) maturation in patient HNSCC tumors. Mature TLS (mTLS) were enriched for stem-like and functional CD8+ T cells, CD4+ Texprog/Tfh cells, and diverse subtypes of B cells and plasma cells. Immature TLS displayed an enrichment of B cells without concurrent plasma cells. Spatial transcriptomics confirmed the presence of triads of CD4+ Texprog/Tfh cells with DCs and B cells, suggesting mTLSs have a role in B cell maturation and effector memory CD8+ T cell generation. The presence of mTLSs was associated with response to ICB therapy in HNSCC.
Contributed by Shishir Pant
(1) Li H (2) Zhang MJ (3) Zhang B (4) Lin WP (5) Li SJ (6) Xiong D (7) Wang Q (8) Wang WD (9) Yang QC (10) Huang CF (11) Deng WW (12) Sun ZJ
Li and Zhang et al. reported the presence of stem-like T cells and B cells at various stages of tertiary lymphoid structure (TLS) maturation in patient HNSCC tumors. Mature TLS (mTLS) were enriched for stem-like and functional CD8+ T cells, CD4+ Texprog/Tfh cells, and diverse subtypes of B cells and plasma cells. Immature TLS displayed an enrichment of B cells without concurrent plasma cells. Spatial transcriptomics confirmed the presence of triads of CD4+ Texprog/Tfh cells with DCs and B cells, suggesting mTLSs have a role in B cell maturation and effector memory CD8+ T cell generation. The presence of mTLSs was associated with response to ICB therapy in HNSCC.
Contributed by Shishir Pant
ABSTRACT: Tumor tertiary lymphoid structures (TLS), especially mature TLS (mTLS), have been associated with better prognosis and improved responses to immune checkpoint blockade (ICB), but the underlying mechanisms remain incompletely understood. Here, by performing single-cell RNA, antigen receptor sequencing and spatial transcriptomics on tumor tissue from head and neck squamous cell carcinoma (HNSCC) patients with different statuses of TLS, we observe that mTLS are enriched with stem-like T cells, and B cells at various maturation stages. Notably, progenitor exhausted CD4(+) T cells, with features resembling follicular helper T cells, support these responses, by activating B cells to produce plasma cells in the germinal center, and interacting with DC-LAMP(+) dendritic cells to support CD8(+) T cell activation. Conversely, non-mTLS tumors do not promote local anti-tumor immunity which is abundant of immunosuppressive cells or a lack of stem-like B and T cells. Furthermore, patients with mTLS manifest improved overall survival and response to ICB compared to those with non-mTLS. Overall, our study provides insights into mechanisms underlying mTLS-mediated intra-tumoral immunity events against cancer.
Author Info: (1) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, Sch
Author Info: (1) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. Department of Oral Maxillofacial-Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. (2) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (3) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (4) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (5) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (6) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (7) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (8) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (9) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (10) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (11) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. dww@whu.edu.cn. Department of Oral Maxillofacial-Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. dww@whu.edu.cn. (12) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. sunzj@whu.edu.cn. Department of Oral Maxillofacial-Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. sunzj@whu.edu.cn.
Citation: Nat Commun 2025 May 7 16:4228 Epub05/07/2025
Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/40335494