Details

Autor(en) / Beteiligte

• Diskin, Brian
• Adam, Salma
• Cassini, Marcelo F
• Sanchez, Gustavo
• Liria, Miguel
• Aykut, Berk
• Buttar, Chandan
• Li, Eric
• Sundberg, Belen
• Salas, Ruben D
• Chen, Ruonan
• Wang, Junjie
• Kim, Mirhee
• Farooq, Mohammad Saad
• Nguy, Susanna
• Fedele, Carmine
• Tang, Kwan Ho
• Chen, Ting
• Wang, Wei
• Hundeyin, Mautin
• Rossi, Juan A Kochen
• Kurz, Emma
• Haq, Muhammad Israr Ul
• Karlen, Jason
• Kruger, Emma
• Sekendiz, Zennur
• Wu, Dongling
• Shadaloey, Sorin A A
• Baptiste, Gillian
• Werba, Gregor
• Selvaraj, Shanmugapriya
• Loomis, Cynthia
• Wong, Kwok-Kin
• Leinwand, Joshua
• Miller, George

Titel

PD-L1 engagement on T cells promotes self-tolerance and suppression of neighboring macrophages and effector T cells in cancer

Ist Teil von

• Nature immunology, 2020-04, Vol.21 (4), p.442-454

Ort / Verlag

United States

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 T 1-polarization and directed T 17-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.