Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy.
Programmed death receptor ligand 1 (PD-L1, also called B7-H1) is a recently described B7 family member. In contrast to B7-1 and B7-2, PD-L1 does not interact with either CD28 or CTLA-4. To date, one specific receptor has been identified that can be ligated by PD-L1. This receptor, programmed death receptor 1 (PD-1), has been shown to negatively regulate T-cell receptor (TCR) signaling. Upon ligating its receptor, PD-L1 has been reported to decrease TCR-mediated proliferation and cytokine production. PD-1 gene-deficient mice developed autoimmune diseases, which early led to the hypothesis of PD-L1 regulating peripheral tolerance. In contrast to normal tissues, which show minimal surface expression of PD-L1 protein, PD-L1 expression was found to be abundant on many murine and human cancers and could be further up-regulated upon IFN-gamma stimulation. Thus, PD-L1 might play an important role in tumor immune evasion. This review discusses the currently available data concerning negative T-cell regulation via PD-1, the blockade of PD-L1/PD-1 interactions, and the implications for adoptive T-cell therapies.
Blank
Christian
C
Department of Hematology and Oncology, University of Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany. christian.blank@klinik.uni-regensburg.de
Gajewski
Thomas F
TF
Mackensen
Andreas
A
D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen / Q000276:immunology*; D060890:B7-H1 Antigen; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000502:physiology; D008562:Membrane Glycoproteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010455:Peptides / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D008562:Membrane Glycoproteins; C105992:PDCD1 protein, human; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor