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:	Min Yu, Sheng Chen, Zi Yin, Tingting Ma, Chuanzhao Zhang, Shanzhou Huang, Mohammad Reza Karimzadeh, Amir Abaas Momtazi-Borojeni
Formato:	article
Lenguaje:	EN
Publicado:	BMJ Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/7cc2dc4dcc8d40598ab784c274122ca0
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spelling	oai:doaj.org-article:7cc2dc4dcc8d40598ab784c274122ca02021-11-16T06:00:05ZMechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L110.1136/jitc-2020-0016982051-1426https://doaj.org/article/7cc2dc4dcc8d40598ab784c274122ca02021-01-01T00:00:00Zhttps://jitc.bmj.com/content/9/1/e001698.fullhttps://doaj.org/toc/2051-1426Exosomes, 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.Min YuSheng ChenZi YinTingting MaChuanzhao ZhangShanzhou HuangMohammad Reza KarimzadehAmir Abaas Momtazi-BorojeniBMJ Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal for ImmunoTherapy of Cancer, Vol 9, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Min Yu Sheng Chen Zi Yin Tingting Ma Chuanzhao Zhang Shanzhou Huang Mohammad Reza Karimzadeh Amir Abaas Momtazi-Borojeni Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1
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.
format	article
author	Min Yu Sheng Chen Zi Yin Tingting Ma Chuanzhao Zhang Shanzhou Huang Mohammad Reza Karimzadeh Amir Abaas Momtazi-Borojeni
author_facet	Min Yu Sheng Chen Zi Yin Tingting Ma Chuanzhao Zhang Shanzhou Huang Mohammad Reza Karimzadeh Amir Abaas Momtazi-Borojeni
author_sort	Min Yu
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_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_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_sort	mechanisms underlying low-clinical responses to pd-1/pd-l1 blocking antibodies in immunotherapy of cancer: a key role of exosomal pd-l1
publisher	BMJ Publishing Group
publishDate	2021
url	https://doaj.org/article/7cc2dc4dcc8d40598ab784c274122ca0
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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

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