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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Main Authors: Sergio Ayala-Mar, Javier Donoso-Quezada, José González-Valdez
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2021/8839978
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author Sergio Ayala-Mar
Javier Donoso-Quezada
José González-Valdez
author_facet Sergio Ayala-Mar
Javier Donoso-Quezada
José González-Valdez
author_sort Sergio Ayala-Mar
collection DOAJ
description 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.
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spelling doaj-art-4e0223ed745740a7a2b595ac4ab7a8012025-08-20T03:36:41ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/88399788839978Clinical Implications of Exosomal PD-L1 in Cancer ImmunotherapySergio Ayala-Mar0Javier Donoso-Quezada1José González-Valdez2Tecnologico de Monterrey, School of Engineering and Science, Av. Eugenio Garza Sada 2501 Sur, Monterrey, NL, MexicoTecnologico de Monterrey, School of Engineering and Science, Av. Eugenio Garza Sada 2501 Sur, Monterrey, NL, MexicoTecnologico de Monterrey, School of Engineering and Science, Av. Eugenio Garza Sada 2501 Sur, Monterrey, NL, MexicoInhibiting 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.http://dx.doi.org/10.1155/2021/8839978
spellingShingle Sergio Ayala-Mar
Javier Donoso-Quezada
José González-Valdez
Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy
Journal of Immunology Research
title Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy
title_full Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy
title_fullStr Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy
title_full_unstemmed Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy
title_short Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy
title_sort clinical implications of exosomal pd l1 in cancer immunotherapy
url http://dx.doi.org/10.1155/2021/8839978
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