Cancer-Associated Fibroblasts Promote the Upregulation of PD-L1 Expression Through Akt Phosphorylation in Colorectal Cancer

Upregulation of immune checkpoint proteins is one of the main mechanisms for tumor immune escape. The expression of programmed death ligand-1 (PD-L1) in colorectal cancer (CRC) is higher than in normal colorectal epithelial tissue, and patients with higher PD-L1 expression have a poorer prognosis. A...

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Autores principales:	Yang Gao, Zhao Sun, Junjie Gu, Zhe Li, Xiuxiu Xu, Chunling Xue, Xuechun Li, Lin Zhao, Jianfeng Zhou, Chunmei Bai, Qin Han, Robert Chunhua Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	colorectal cancer cancer-associated fibroblasts PD-L1 Akt phosphorylation immune escape Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e34b2dc6c5254c04845e543dc93fbe09
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spelling	oai:doaj.org-article:e34b2dc6c5254c04845e543dc93fbe092021-11-19T05:57:41ZCancer-Associated Fibroblasts Promote the Upregulation of PD-L1 Expression Through Akt Phosphorylation in Colorectal Cancer2234-943X10.3389/fonc.2021.748465https://doaj.org/article/e34b2dc6c5254c04845e543dc93fbe092021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.748465/fullhttps://doaj.org/toc/2234-943XUpregulation of immune checkpoint proteins is one of the main mechanisms for tumor immune escape. The expression of programmed death ligand-1 (PD-L1) in colorectal cancer (CRC) is higher than in normal colorectal epithelial tissue, and patients with higher PD-L1 expression have a poorer prognosis. Additionally, PD-L1 expression in CRC is affected by the tumor microenvironment (TME). As a major component of the TME, cancer-associated fibroblasts (CAFs) can act as immune regulators and generate an immunosuppressive tumor microenvironment. Therefore, we speculated that CAFs may be related to the upregulation of PD-L1 in CRC, which leads to tumor immune escape. We found that CAFs upregulate PD-L1 expression in CRC cells through AKT phosphorylation, thereby reducing the killing of CRC cells by peripheral blood mononuclear cells. The ratio of CAFs to CRC cells was positively correlated with AKT phosphorylation and the expression of PD-L1 in CRC in vitro. Consistent with the in vitro results, high CAF content and high expression of PD-L1 were negatively correlated with disease-free survival (DFS) of CRC patients. These results indicate that the upregulation of PD-L1 expression in CRC by CAFs through the activation of Akt is one of the molecular mechanisms of tumor immune escape. Thus, targeted anti-CAF therapy may help improve the efficacy of immunotherapy.Yang GaoZhao SunJunjie GuZhe LiXiuxiu XuChunling XueXuechun LiLin ZhaoJianfeng ZhouChunmei BaiQin HanRobert Chunhua ZhaoRobert Chunhua ZhaoFrontiers Media S.A.articlecolorectal cancercancer-associated fibroblastsPD-L1Akt phosphorylationimmune escapeNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer cancer-associated fibroblasts PD-L1 Akt phosphorylation immune escape Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	colorectal cancer cancer-associated fibroblasts PD-L1 Akt phosphorylation immune escape Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yang Gao Zhao Sun Junjie Gu Zhe Li Xiuxiu Xu Chunling Xue Xuechun Li Lin Zhao Jianfeng Zhou Chunmei Bai Qin Han Robert Chunhua Zhao Robert Chunhua Zhao Cancer-Associated Fibroblasts Promote the Upregulation of PD-L1 Expression Through Akt Phosphorylation in Colorectal Cancer
description	Upregulation of immune checkpoint proteins is one of the main mechanisms for tumor immune escape. The expression of programmed death ligand-1 (PD-L1) in colorectal cancer (CRC) is higher than in normal colorectal epithelial tissue, and patients with higher PD-L1 expression have a poorer prognosis. Additionally, PD-L1 expression in CRC is affected by the tumor microenvironment (TME). As a major component of the TME, cancer-associated fibroblasts (CAFs) can act as immune regulators and generate an immunosuppressive tumor microenvironment. Therefore, we speculated that CAFs may be related to the upregulation of PD-L1 in CRC, which leads to tumor immune escape. We found that CAFs upregulate PD-L1 expression in CRC cells through AKT phosphorylation, thereby reducing the killing of CRC cells by peripheral blood mononuclear cells. The ratio of CAFs to CRC cells was positively correlated with AKT phosphorylation and the expression of PD-L1 in CRC in vitro. Consistent with the in vitro results, high CAF content and high expression of PD-L1 were negatively correlated with disease-free survival (DFS) of CRC patients. These results indicate that the upregulation of PD-L1 expression in CRC by CAFs through the activation of Akt is one of the molecular mechanisms of tumor immune escape. Thus, targeted anti-CAF therapy may help improve the efficacy of immunotherapy.
format	article
author	Yang Gao Zhao Sun Junjie Gu Zhe Li Xiuxiu Xu Chunling Xue Xuechun Li Lin Zhao Jianfeng Zhou Chunmei Bai Qin Han Robert Chunhua Zhao Robert Chunhua Zhao
author_facet	Yang Gao Zhao Sun Junjie Gu Zhe Li Xiuxiu Xu Chunling Xue Xuechun Li Lin Zhao Jianfeng Zhou Chunmei Bai Qin Han Robert Chunhua Zhao Robert Chunhua Zhao
author_sort	Yang Gao
title	Cancer-Associated Fibroblasts Promote the Upregulation of PD-L1 Expression Through Akt Phosphorylation in Colorectal Cancer
title_short	Cancer-Associated Fibroblasts Promote the Upregulation of PD-L1 Expression Through Akt Phosphorylation in Colorectal Cancer
title_full	Cancer-Associated Fibroblasts Promote the Upregulation of PD-L1 Expression Through Akt Phosphorylation in Colorectal Cancer
title_fullStr	Cancer-Associated Fibroblasts Promote the Upregulation of PD-L1 Expression Through Akt Phosphorylation in Colorectal Cancer
title_full_unstemmed	Cancer-Associated Fibroblasts Promote the Upregulation of PD-L1 Expression Through Akt Phosphorylation in Colorectal Cancer
title_sort	cancer-associated fibroblasts promote the upregulation of pd-l1 expression through akt phosphorylation in colorectal cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e34b2dc6c5254c04845e543dc93fbe09
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Cancer-Associated Fibroblasts Promote the Upregulation of PD-L1 Expression Through Akt Phosphorylation in Colorectal Cancer

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