PD-L1 engagement on T cells promotes self-tolerance and suppression of neighboring macrophages and effector T cells in cancer
| Autor: | Gillian G. Baptiste, Belen Sundberg, Mirhee Kim, Joshua Leinwand, Zennur Sekendiz, Juan A. Kochen Rossi, Ruben D. Salas, Emma Kurz, Gregor Werba, Sorin A. A. Shadaloey, George Miller, Ruonan Chen, Berk Aykut, Shanmugapriya Selvaraj, Kwan Ho Tang, Miguel Liria, Emma Kruger, Susanna Nguy, Carmine Fedele, Salma Adam, Eric Li, Jason Karlen, Gustavo Sanchez, Dongling Wu, Chandan Buttar, Kwok-Kin Wong, Brian Diskin, Ting Chen, Wei Wang, Mautin Hundeyin, Junjie Wang, Cynthia Loomis, Muhammad Israr Ul Haq, Mohammad Saad Farooq, Marcelo F. Cassini |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male medicine.medical_treatment T cell Immunology Programmed Cell Death 1 Receptor CD8-Positive T-Lymphocytes medicine.disease_cause B7-H1 Antigen 03 medical and health sciences Interferon-gamma Mice 0302 clinical medicine Cancer immunotherapy PD-L1 Cell Line Tumor medicine Immune Tolerance Tumor Microenvironment Immunology and Allergy Animals Humans biology Chemistry Effector Macrophages Cell Differentiation Tumor antigen Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Self Tolerance Cell culture biology.protein Female Carcinogenesis CD8 030215 immunology Signal Transduction |
| Zdroj: | Nature immunology. 21(4) |
| ISSN: | 1529-2916 |
| Popis: | Programmed cell death protein 1 (PD-1) ligation delimits immunogenic responses in T cells. However, the consequences of programmed cell death 1 ligand 1 (PD-L1) ligation in T cells are uncertain. We found that T cell expression of PD-L1 in cancer was regulated by tumor antigen and sterile inflammatory cues. PD-L1+ T cells exerted tumor-promoting tolerance via three distinct mechanisms: (1) binding of PD-L1 induced STAT3-dependent 'back-signaling' in CD4+ T cells, which prevented activation, reduced TH1-polarization and directed TH17-differentiation. PD-L1 signaling also induced an anergic T-bet-IFN-γ- phenotype in CD8+ T cells and was equally suppressive compared to PD-1 signaling; (2) PD-L1+ T cells restrained effector T cells via the canonical PD-L1-PD-1 axis and were sufficient to accelerate tumorigenesis, even in the absence of endogenous PD-L1; (3) PD-L1+ T cells engaged PD-1+ macrophages, inducing an alternative M2-like program, which had crippling effects on adaptive antitumor immunity. Collectively, we demonstrate that PD-L1+ T cells have diverse tolerogenic effects on tumor immunity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink