Regulation and Function of the PD-L1 Checkpoint

By Chong Sun, R. Mezzadra, Ton N. Schumacher. Immunity, 2018

1,861 citations recorded by the source corpus.

Expression of programmed death-ligand 1 (PD-L1) is frequently observed in human cancers. Binding of PD-L1 to its receptor PD-1 on activated T cells inhibits anti-tumor immunity by counteracting T cell-activating signals. Antibody-based PD-1-PD-L1 inhibitors can induce durable tumor remissions in patients with diverse advanced cancers, and thus expression of PD-L1 on tumor cells and other cells in the tumor microenviroment is of major clinical relevance. Here we review the roles of the PD-1-PD-L1 axis in cancer, focusing on recent findings on the mechanisms that regulate PD-L1 expression at the transcriptional, posttranscriptional, and protein level. We place this knowledge in the context of observations in the clinic and discuss how it may inform the design of more precise and effective cancer immune checkpoint therapies.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/7289dad4472f63d04b5019c25d5bc2c28e1d1652

How researchers see this paper

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In Immunology

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In Oncology

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Citations in the corpus

• Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors (2018, background): “Therefore, total PD-L1 including IFN-γ-derived and IFN-γ-independent PD-L1 is not accurate to reflect tumor immune surveillance status [115].”
• Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy (2022, background): “Traditionally, it was believed that immunotherapyactivated CD8+ T cells induce tumor cell death mainly through the perforin-granzyme pathway and the Fas-Fas ligand (FASL) pathway.(26,27) However, many studies have surprisingly revealed that CD8+ T cells can suppress tumors by inducing ferroptosis an”
• Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives (2021, background): “The binding of PD-L1 to its receptor PD-1 on activated T cells hampers antitumor immunity by counteracting T cell-activating signals [252].”
• Mechanisms controlling PD-L1 expression in cancer (2019, background): “Elucidating the roles of oncogenic pathways driving PD-L1 expression not only identifies the functional mechanisms but also offers a rationale for future combination therapy consisting immune checkpoint blockade antibodies and inhibitors targeting those oncogenic signaling pathways (Sanmamed and Che”