Abstract
The use of immune checkpoint therapies targeting programmed death-1 (PD-1) and its ligand (PD-L1) continue to show limited durable success in clinical cases despite widespread application. While some patients achieve complete responses and disease remission, others are completely resistant to the therapy. Recent evidence in the field suggests that tumor-derived exosomes could be responsible for mediating systemic immunosuppression that antagonizes anti-PD-1 checkpoint therapy. In this Opinion article, we discuss our claim that endogenous tumor exosomal PD-L1 and tumor-derived exosome-induced PD-L1 are two of the most notable mechanisms of exosome-mediated resistance against antitumor immunity and we discuss how this resistance could directly influence immune checkpoint therapy failure.
Keywords:
PD-L1; exosomes; immunotherapy.
Copyright © 2020 Elsevier Inc. All rights reserved.
MeSH terms
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Animals
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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B7-H1 Antigen / antagonists & inhibitors
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B7-H1 Antigen / immunology
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B7-H1 Antigen / metabolism*
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Disease Progression
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Drug Resistance, Neoplasm / drug effects
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Drug Resistance, Neoplasm / immunology
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Exosomes / drug effects
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Exosomes / immunology
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Exosomes / metabolism*
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Humans
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Immune Checkpoint Inhibitors / pharmacology
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Immune Checkpoint Inhibitors / therapeutic use
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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Neoplasms / drug therapy*
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Neoplasms / immunology
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T-Lymphocytes, Cytotoxic / immunology
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Treatment Failure
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Tumor Burden / drug effects
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Tumor Burden / immunology
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Tumor Escape / drug effects
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Tumor Microenvironment / drug effects
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Tumor Microenvironment / immunology*
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Xenograft Model Antitumor Assays
Substances
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B7-H1 Antigen
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CD274 protein, human
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Cd274 protein, mouse
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Immune Checkpoint Inhibitors