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The Extrinsic and Intrinsic Roles of PD-L1 and Its Receptor PD-1: Implications for Immunotherapy Treatment
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The Extrinsic and Intrinsic Roles of PD-L1 and Its Receptor PD-1: Implications for Immunotherapy Treatment
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Journal Article
The Extrinsic and Intrinsic Roles of PD-L1 and Its Receptor PD-1: Implications for Immunotherapy Treatment
2020
Overview
Programmed death-ligand 1 (PD-L1) is an immune checkpoint inhibitor that binds to its receptor PD-1 expressed by T cells and other immune cells to regulate immune responses; ultimately preventing exacerbated activation and autoimmunity. Many tumors exploit this mechanism by overexpressing PD-L1 which often correlates with poor prognosis. Some tumors have also recently been shown to express PD-1. On tumors, PD-L1 binding to PD-1 on immune cells promotes immune evasion and tumor progression, primarily by inhibition of cytotoxic T lymphocyte effector function. PD-1/PD-L1-targeted therapy has revolutionized the cancer therapy landscape and has become the first-line treatment for some cancers, due to their ability to promote durable anti-tumor immune responses in select patients with advanced cancers. Despite this clinical success, some patients have shown to be unresponsive, hyperprogressive or develop resistance to PD-1/PD-L1-targeted therapy. The exact mechanisms for this are still unclear. This review will discuss the current status of PD-1/PD-L1-targeted therapy, oncogenic expression of PD-L1, the new and emerging tumor-intrinisic roles of PD-L1 and its receptor PD-1 and how they may contribute to tumor progression and immunotherapy responses as shown in different oncology models.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
/ Antigens
/ Antineoplastic Agents - immunology
/ Antineoplastic Agents - therapeutic use
/ Editing
/ Epigenesis, Genetic - drug effects
/ Gene Expression Regulation, Neoplastic - drug effects
/ Humans
/ Immune checkpoint inhibitors
/ Immune Checkpoint Inhibitors - pharmacology
/ Immune Checkpoint Inhibitors - therapeutic use
/ Immunomodulation - drug effects
/ Ligands
/ Melanoma
/ Mutation
/ novel therapeutic strategies
/ Patients
/ Programmed Cell Death 1 Receptor - genetics
/ Programmed Cell Death 1 Receptor - metabolism
/ Signal Transduction - drug effects
/ Tumors
