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Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1

Exosomes, as the main group of extracellular vesicles, are biologically active lipid-bilayer vesicles that are naturally released from different types of normal or tumor cells. These vesicles play an important role in intercellular communication and influence the extracellular environment and the im...

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Autores principales: Yin, Zi, Yu, Min, Ma, Tingting, Zhang, Chuanzhao, Huang, Shanzhou, Karimzadeh, Mohammad Reza, Momtazi-Borojeni, Amir Abaas, Chen, Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818841/
https://www.ncbi.nlm.nih.gov/pubmed/33472857
http://dx.doi.org/10.1136/jitc-2020-001698
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author Yin, Zi
Yu, Min
Ma, Tingting
Zhang, Chuanzhao
Huang, Shanzhou
Karimzadeh, Mohammad Reza
Momtazi-Borojeni, Amir Abaas
Chen, Sheng
author_facet Yin, Zi
Yu, Min
Ma, Tingting
Zhang, Chuanzhao
Huang, Shanzhou
Karimzadeh, Mohammad Reza
Momtazi-Borojeni, Amir Abaas
Chen, Sheng
author_sort Yin, Zi
collection PubMed
description Exosomes, as the main group of extracellular vesicles, are biologically active lipid-bilayer vesicles that are naturally released from different types of normal or tumor cells. These vesicles play an important role in intercellular communication and influence the extracellular environment and the immune system. Emerging evidence demonstrates that cancer-derived exosomes are enriched in immunosuppressive proteins, such as the programmed death-ligand 1 (PD-L1). PD-L1 and its receptor programmed cell death protein 1 (PD-1) are the key immune checkpoint molecules that promote tumor progression via negative regulation of immune responses. PDL-1 is highly expressed on the surface of tumor cells and binds to PD-1 on the surface of activated T cells, leading to suppression of T cells, which consequently enables cancer cells to escape antitumor immunity. Currently, there are several Food and Drug Administration-approved monoclonal antibodies blocking PD-1/PD-L1 interaction, which are clinically used for cancer treatment. However, despite impressive treatment outcomes, some patients show poor response to PD-1/PD-L1 blockade. Of note, tumor-derived exosomes containing PD-L1 can recapitulate the effect of cell-surface PD-L1. There is evidence that reveals a significant association between levels of circulating exosomal PD-L1 and rate of response to anti-PD-1/PD-L1 antibody therapy. The present article reviews the role of exosomal PDL-1 in the therapeutic resistance to anti-PD-1/PD-L1 treatment. Importantly, it is suggested that the removal of exosomal PDL-1 could serve as a therapeutic adjuvant for enhancing the efficacy of anti-PD-1/PD-L1 therapy in patients with cancer.
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spelling pubmed-78188412021-01-25 Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1 Yin, Zi Yu, Min Ma, Tingting Zhang, Chuanzhao Huang, Shanzhou Karimzadeh, Mohammad Reza Momtazi-Borojeni, Amir Abaas Chen, Sheng J Immunother Cancer Review Exosomes, as the main group of extracellular vesicles, are biologically active lipid-bilayer vesicles that are naturally released from different types of normal or tumor cells. These vesicles play an important role in intercellular communication and influence the extracellular environment and the immune system. Emerging evidence demonstrates that cancer-derived exosomes are enriched in immunosuppressive proteins, such as the programmed death-ligand 1 (PD-L1). PD-L1 and its receptor programmed cell death protein 1 (PD-1) are the key immune checkpoint molecules that promote tumor progression via negative regulation of immune responses. PDL-1 is highly expressed on the surface of tumor cells and binds to PD-1 on the surface of activated T cells, leading to suppression of T cells, which consequently enables cancer cells to escape antitumor immunity. Currently, there are several Food and Drug Administration-approved monoclonal antibodies blocking PD-1/PD-L1 interaction, which are clinically used for cancer treatment. However, despite impressive treatment outcomes, some patients show poor response to PD-1/PD-L1 blockade. Of note, tumor-derived exosomes containing PD-L1 can recapitulate the effect of cell-surface PD-L1. There is evidence that reveals a significant association between levels of circulating exosomal PD-L1 and rate of response to anti-PD-1/PD-L1 antibody therapy. The present article reviews the role of exosomal PDL-1 in the therapeutic resistance to anti-PD-1/PD-L1 treatment. Importantly, it is suggested that the removal of exosomal PDL-1 could serve as a therapeutic adjuvant for enhancing the efficacy of anti-PD-1/PD-L1 therapy in patients with cancer. BMJ Publishing Group 2021-01-20 /pmc/articles/PMC7818841/ /pubmed/33472857 http://dx.doi.org/10.1136/jitc-2020-001698 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Review
Yin, Zi
Yu, Min
Ma, Tingting
Zhang, Chuanzhao
Huang, Shanzhou
Karimzadeh, Mohammad Reza
Momtazi-Borojeni, Amir Abaas
Chen, Sheng
Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1
title Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1
title_full Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1
title_fullStr Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1
title_full_unstemmed Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1
title_short Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1
title_sort mechanisms underlying low-clinical responses to pd-1/pd-l1 blocking antibodies in immunotherapy of cancer: a key role of exosomal pd-l1
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818841/
https://www.ncbi.nlm.nih.gov/pubmed/33472857
http://dx.doi.org/10.1136/jitc-2020-001698
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