Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion.
Recent clinical data support ideas of Programmed death receptor-ligand 1 (PD-L1; also called B7-H1, CD274) playing an important role in immune evasion of tumor cells. Expression of PD-L1 on tumors strongly correlates with the survival of cancer patients. PD-L1 on tumors interacts with the co-inhibitory molecule Programmed death receptor-1 (PD-1, CD279) on T cells mediating decreased TCR-mediated proliferation and cytokine production. In animal tumor models, blockade of PD-L1/PD-1 interactions resulted in an improved tumor control. In addition, exhausted T cells during chronic viral infections could be revived by PD-L1 blockade. Thus, targeting PD-L1/PD-1 interactions might improve the efficacy of adoptive cell therapies (ACT) of chronic infections as well as cancers. Obstacles for a general blockade of PD-L1 might be its role in mediating peripheral tolerance. This review discusses the currently available data concerning the role of PD-L1 in tumor immune evasion and envisions possibilities for implementation into ACT for cancer patients.
Blank
Christian
C
Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany. christian.blank@klinik.uni-regensburg.de
Mackensen
Andreas
A
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000276:immunology*; D060890:B7-H1 Antigen; D006801:Humans; D016219:Immunotherapy, Adoptive; D007239:Infections / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor; D013601:T-Lymphocytes / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology*
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor