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Pan-cancer mapping of single CD8+ T cell profiles reveals a TCF1:CXCR6 axis regulating CD28 co-stimulation and anti-tumor immunity.
Tooley, Katherine; Jerby, Livnat; Escobar, Giulia; Krovi, S Harsha; Mangani, Davide; Dandekar, Gitanjali; Cheng, Hanning; Madi, Asaf; Goldschmidt, Ella; Lambden, Conner; Krishnan, Rajesh K; Rozenblatt-Rosen, Orit; Regev, Aviv; Anderson, Ana C.
Afiliação
  • Tooley K; The Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA; Division of Medical Sciences, Harvard Medical School, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Ho
  • Jerby L; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: ljerby@stanford.edu.
  • Escobar G; The Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Krovi SH; The Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Mangani D; The Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Dandekar G; The Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Cheng H; The Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Madi A; Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Goldschmidt E; Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Lambden C; The Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Krishnan RK; The Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Regev A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute and Koch Institute of Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: regev.aviv@gene.com.
  • Anderson AC; The Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:
Cell Rep Med ; 5(7): 101640, 2024 Jul 16.
Article em En | MEDLINE | ID: mdl-38959885
ABSTRACT
CD8+ T cells must persist and function in diverse tumor microenvironments to exert their effects. Thus, understanding common underlying expression programs could better inform the next generation of immunotherapies. We apply a generalizable matrix factorization algorithm that recovers both shared and context-specific expression programs from diverse datasets to a single-cell RNA sequencing (scRNA-seq) compendium of 33,161 CD8+ T cells from 132 patients with seven human cancers. Our meta-single-cell analyses uncover a pan-cancer T cell dysfunction program that predicts clinical non-response to checkpoint blockade in melanoma and highlights CXCR6 as a pan-cancer marker of chronically activated T cells. Cxcr6 is trans-activated by AP-1 and repressed by TCF1. Using mouse models, we show that Cxcr6 deletion in CD8+ T cells increases apoptosis of PD1+TIM3+ cells, dampens CD28 signaling, and compromises tumor growth control. Our study uncovers a TCF1CXCR6 axis that counterbalances PD1-mediated suppression of CD8+ cell responses and is essential for effective anti-tumor immunity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígenos CD28 / Linfócitos T CD8-Positivos / Fator 1-alfa Nuclear de Hepatócito / Receptores CXCR6 Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígenos CD28 / Linfócitos T CD8-Positivos / Fator 1-alfa Nuclear de Hepatócito / Receptores CXCR6 Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article