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Tumor-derived exosomes induce PD1(+) macrophage population in human gastric cancer that promotes disease progression
Macrophages constitute a major component of tumor-infiltrating immune cells. M2 macrophages have been reported to promote tumor progression through promoting tumor angiogenesis and metastasis and regulating T-cell function. Here, we identified a protumorigenic subset of macrophages that constitutive...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968036/ https://www.ncbi.nlm.nih.gov/pubmed/29799520 http://dx.doi.org/10.1038/s41389-018-0049-3 |
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author | Wang, Furong Li, Bin Wei, Yucai Zhao, Yang Wang, Li Zhang, Peng Yang, Jinwei He, Wenting Chen, Hao Jiao, Zuoyi Li, Yumin |
author_facet | Wang, Furong Li, Bin Wei, Yucai Zhao, Yang Wang, Li Zhang, Peng Yang, Jinwei He, Wenting Chen, Hao Jiao, Zuoyi Li, Yumin |
author_sort | Wang, Furong |
collection | PubMed |
description | Macrophages constitute a major component of tumor-infiltrating immune cells. M2 macrophages have been reported to promote tumor progression through promoting tumor angiogenesis and metastasis and regulating T-cell function. Here, we identified a protumorigenic subset of macrophages that constitutively expressed programmed cell death 1 (PD1) and accumulated in advanced-stage gastric cancer (GC). These PD1(+) tumor-associated macrophages (TAMs) exhibited an M2-like surface profile, with a significant increase in the expression of CD206, IL-10, and CCL1, and a clear decrease in the expression of MHC class II, CD64, and IL-12 and the ability to phagocytose ovalbumin. Moreover, PD1(+) TAMs can suppress CD8(+) T-cell function and this immunosuppressive activity can effectively be enhanced upon triggering PD1 signal. GC-derived exosomes effectively educated monocytes to differentiate into PD1(+) TAMs with M2 phenotypic and functional characteristics. Together, our results are the first to show that GC-derived exosomes can effectively induce PD1(+) TAM generation, and these cells can produce a large number of IL-10, impair CD8(+) T-cell function, and thereby create conditions that promote GC progression. Thus, methods in which immunotherapy is combined with targeting PD1(+) TAMs and tumor-derived exosomes should be used to restore immune function in GC patients. |
format | Online Article Text |
id | pubmed-5968036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59680362018-05-25 Tumor-derived exosomes induce PD1(+) macrophage population in human gastric cancer that promotes disease progression Wang, Furong Li, Bin Wei, Yucai Zhao, Yang Wang, Li Zhang, Peng Yang, Jinwei He, Wenting Chen, Hao Jiao, Zuoyi Li, Yumin Oncogenesis Article Macrophages constitute a major component of tumor-infiltrating immune cells. M2 macrophages have been reported to promote tumor progression through promoting tumor angiogenesis and metastasis and regulating T-cell function. Here, we identified a protumorigenic subset of macrophages that constitutively expressed programmed cell death 1 (PD1) and accumulated in advanced-stage gastric cancer (GC). These PD1(+) tumor-associated macrophages (TAMs) exhibited an M2-like surface profile, with a significant increase in the expression of CD206, IL-10, and CCL1, and a clear decrease in the expression of MHC class II, CD64, and IL-12 and the ability to phagocytose ovalbumin. Moreover, PD1(+) TAMs can suppress CD8(+) T-cell function and this immunosuppressive activity can effectively be enhanced upon triggering PD1 signal. GC-derived exosomes effectively educated monocytes to differentiate into PD1(+) TAMs with M2 phenotypic and functional characteristics. Together, our results are the first to show that GC-derived exosomes can effectively induce PD1(+) TAM generation, and these cells can produce a large number of IL-10, impair CD8(+) T-cell function, and thereby create conditions that promote GC progression. Thus, methods in which immunotherapy is combined with targeting PD1(+) TAMs and tumor-derived exosomes should be used to restore immune function in GC patients. Nature Publishing Group UK 2018-05-25 /pmc/articles/PMC5968036/ /pubmed/29799520 http://dx.doi.org/10.1038/s41389-018-0049-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Furong Li, Bin Wei, Yucai Zhao, Yang Wang, Li Zhang, Peng Yang, Jinwei He, Wenting Chen, Hao Jiao, Zuoyi Li, Yumin Tumor-derived exosomes induce PD1(+) macrophage population in human gastric cancer that promotes disease progression |
title | Tumor-derived exosomes induce PD1(+) macrophage population in human gastric cancer that promotes disease progression |
title_full | Tumor-derived exosomes induce PD1(+) macrophage population in human gastric cancer that promotes disease progression |
title_fullStr | Tumor-derived exosomes induce PD1(+) macrophage population in human gastric cancer that promotes disease progression |
title_full_unstemmed | Tumor-derived exosomes induce PD1(+) macrophage population in human gastric cancer that promotes disease progression |
title_short | Tumor-derived exosomes induce PD1(+) macrophage population in human gastric cancer that promotes disease progression |
title_sort | tumor-derived exosomes induce pd1(+) macrophage population in human gastric cancer that promotes disease progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968036/ https://www.ncbi.nlm.nih.gov/pubmed/29799520 http://dx.doi.org/10.1038/s41389-018-0049-3 |
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