Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy

Inhibiting the programmed cell death ligand-1 (PD-L1)/programmed cell death receptor-1 (PD-1) signaling axis reinvigorates the antitumor immune response with remarkable clinical efficacy. Yet, low response rates limit the benefits of immunotherapy to a minority of patients. Recent studies have explo...

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Bibliographic Details
Published in:Journal of immunology research 2021, Vol.2021, p.8839978-18
Main Authors: Ayala-Mar, Sergio, Donoso-Quezada, Javier, González-Valdez, José
Format: Article
Language:English
Subjects:
Antitumor activity
Apoptosis
Biomarkers
Biosynthesis
Breast cancer
Cancer
Cancer immunotherapy
Cell death
Exosomes
Growth factors
Immunology
Immunosuppression
Immunotherapy
Kinases
Lung cancer
Lymphocytes T
Melanoma
Metastasis
Monoclonal antibodies
PD-1 protein
PD-L1 protein
Plasma
Proteins
Review
Tumor microenvironment
Tumor necrosis factor-TNF
Tumors
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Summary:Inhibiting the programmed cell death ligand-1 (PD-L1)/programmed cell death receptor-1 (PD-1) signaling axis reinvigorates the antitumor immune response with remarkable clinical efficacy. Yet, low response rates limit the benefits of immunotherapy to a minority of patients. Recent studies have explored the importance of PD-L1 as a transmembrane protein in exosomes and have revealed exosomal PD-L1 as a mechanism of tumor immune escape and immunotherapy resistance. Exosomal PD-L1 suppresses T cell effector function, induces systemic immunosuppression, and transfers functional PD-L1 across the tumor microenvironment (TME). Because of its significant contribution to immune escape, exosomal PD-L1 has been proposed as a biomarker to predict immunotherapy response and to assess therapeutic efficacy. In this review, we summarize the immunological mechanisms of exosomal PD-L1, focusing on the factors that lead to exosome biogenesis and release. Next, we review the effect of exosomal PD-L1 on T cell function and its role across the TME. In addition, we discuss the latest findings on the use of exosomal PD-L1 as a biomarker for cancer immunotherapy. Throughout this review, we propose exosomal PD-L1 as a critical mediator of tumor progression and highlight the clinical implications that follow for immuno-oncology, discussing the potential to target exosomes to advance cancer treatment.
ISSN:2314-8861
2314-7156
DOI:10.1155/2021/8839978