Mechanisms Controlling PD-L1 Expression in Cancer

The engagement of programmed cell death protein 1 (PD-1; encoded by the PDCD1 gene) receptor expressed on activated T cells and its ligand, programmed death-ligand 1 (PD-L1; encoded by the CD274 gene), is a major co-inhibitory checkpoint signaling that controls T cell activities. Various types of ca...

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Bibliographic Details
Published in:Molecular cell Vol. 76; no. 3; p. 359
Main Authors: Cha, Jong-Ho, Chan, Li-Chuan, Li, Chia-Wei, Hsu, Jennifer L, Hung, Mien-Chie
Format: Journal Article
Language:English
Published: United States 07.11.2019
Subjects:
Animals
Antineoplastic Agents, Immunological - therapeutic use
B7-H1 Antigen - antagonists & inhibitors
B7-H1 Antigen - genetics
B7-H1 Antigen - immunology
B7-H1 Antigen - metabolism
Biomarkers, Tumor - antagonists & inhibitors
Biomarkers, Tumor - genetics
Biomarkers, Tumor - immunology
Biomarkers, Tumor - metabolism
Gene Expression Regulation, Neoplastic
Humans
Molecular Targeted Therapy
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - metabolism
Protein Processing, Post-Translational
RNA Processing, Post-Transcriptional
Signal Transduction
Transcription, Genetic
Tumor Escape
ISSN:1097-4164, 1097-4164
Online Access:Get more information
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Summary:The engagement of programmed cell death protein 1 (PD-1; encoded by the PDCD1 gene) receptor expressed on activated T cells and its ligand, programmed death-ligand 1 (PD-L1; encoded by the CD274 gene), is a major co-inhibitory checkpoint signaling that controls T cell activities. Various types of cancers express high levels of PD-L1 and exploit PD-L1/PD-1 signaling to evade T cell immunity. Blocking the PD-L1/PD-1 pathway has consistently shown remarkable anti-tumor effects in patients with advanced cancers and is recognized as the gold standard for developing new immune checkpoint blockade (ICB) and combination therapies. However, the response rates of anti-PD-L1 have been limited in several solid tumors. Therefore, furthering our understanding of the regulatory mechanisms of PD-L1 can bring substantial benefits to patients with cancer by improving the efficacy of current PD-L1/PD-1 blockade or other ICBs. In this review, we provide current knowledge of PD-L1 regulatory mechanisms at the transcriptional, posttranscriptional, post-translational, and extracellular levels, and discuss the implications of these findings in cancer diagnosis and immunotherapy.
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ISSN:1097-4164
1097-4164
DOI:10.1016/j.molcel.2019.09.030