Tumor-associated neutrophils activated by tumor-derived CCL20 (C-C motif chemokine ligand 20) promote T cell immunosuppression via programmed death-ligand 1 (PD-L1) in breast cancer

Breast cancer is the leading cause of cancer-related death among women despite the significant improvement in diagnosis and treatment. Tumor-associated neutrophils have been shown to suppress antitumor functions of the host. However, how breast cancer tumor microenvironment influences the phenotype...

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Autores principales:	Louis Boafo Kwantwi, Shujing Wang, Wenjun Zhang, Weidong Peng, Zeyu Cai, Youjing Sheng, Han Xiao, Xian Wang, Qiang Wu
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	tumor-associated neutrophils ccl20 pd-l1 immunosuppressive breast cancer Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/444d247b7df34cb1aab09ee007ff3d69
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spelling	oai:doaj.org-article:444d247b7df34cb1aab09ee007ff3d692021-11-26T11:19:49ZTumor-associated neutrophils activated by tumor-derived CCL20 (C-C motif chemokine ligand 20) promote T cell immunosuppression via programmed death-ligand 1 (PD-L1) in breast cancer2165-59792165-598710.1080/21655979.2021.1977102https://doaj.org/article/444d247b7df34cb1aab09ee007ff3d692021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1977102https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Breast cancer is the leading cause of cancer-related death among women despite the significant improvement in diagnosis and treatment. Tumor-associated neutrophils have been shown to suppress antitumor functions of the host. However, how breast cancer tumor microenvironment influences the phenotype and functions of neutrophils to potentiate T cell immunosuppression is unknown. Herein, neutrophils isolated from peripheral blood of healthy donors were treated with supernatants from breast cancer cell lines or recombinant human CCL20. PD-L1 expression on neutrophils was then evaluated by immunofluorescence and flow cytometry. Neutrophils and Jurkat T cells were cocultured to evaluate the effect of tumor-associated neutrophils on T cell functions. Finally, immunohistochemical staining was performed to evaluate the clinical relevance of neutrophils infiltrating breast tumor tissues. Tumor-derived CCL20 activated and upregulated PD-L1 expression on neutrophils. A significant positive correlation was found between CCL20 and CD66b+ neutrophils in tumor tissues. Through in vitro experiment, tumor-associated neutrophils (TANs) effectively suppressed T cell immunity which was reversed upon PD-L1 blockade. Moreover, a high density of TANs was associated with short disease free survival in breast cancer patients. Furthermore, receiver operating curve showed that the density of TANs could accurately predict disease-free survival in breast cancer patients. Our findings suggest that targeting TANs via CCL20 immunosuppressive pathway may be a novel therapeutic strategy for breast cancer treatment.Louis Boafo KwantwiShujing WangWenjun ZhangWeidong PengZeyu CaiYoujing ShengHan XiaoXian WangQiang WuTaylor & Francis Grouparticletumor-associated neutrophilsccl20pd-l1immunosuppressivebreast cancerBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 1, Pp 6996-7006 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tumor-associated neutrophils ccl20 pd-l1 immunosuppressive breast cancer Biotechnology TP248.13-248.65
spellingShingle	tumor-associated neutrophils ccl20 pd-l1 immunosuppressive breast cancer Biotechnology TP248.13-248.65 Louis Boafo Kwantwi Shujing Wang Wenjun Zhang Weidong Peng Zeyu Cai Youjing Sheng Han Xiao Xian Wang Qiang Wu Tumor-associated neutrophils activated by tumor-derived CCL20 (C-C motif chemokine ligand 20) promote T cell immunosuppression via programmed death-ligand 1 (PD-L1) in breast cancer
description	Breast cancer is the leading cause of cancer-related death among women despite the significant improvement in diagnosis and treatment. Tumor-associated neutrophils have been shown to suppress antitumor functions of the host. However, how breast cancer tumor microenvironment influences the phenotype and functions of neutrophils to potentiate T cell immunosuppression is unknown. Herein, neutrophils isolated from peripheral blood of healthy donors were treated with supernatants from breast cancer cell lines or recombinant human CCL20. PD-L1 expression on neutrophils was then evaluated by immunofluorescence and flow cytometry. Neutrophils and Jurkat T cells were cocultured to evaluate the effect of tumor-associated neutrophils on T cell functions. Finally, immunohistochemical staining was performed to evaluate the clinical relevance of neutrophils infiltrating breast tumor tissues. Tumor-derived CCL20 activated and upregulated PD-L1 expression on neutrophils. A significant positive correlation was found between CCL20 and CD66b+ neutrophils in tumor tissues. Through in vitro experiment, tumor-associated neutrophils (TANs) effectively suppressed T cell immunity which was reversed upon PD-L1 blockade. Moreover, a high density of TANs was associated with short disease free survival in breast cancer patients. Furthermore, receiver operating curve showed that the density of TANs could accurately predict disease-free survival in breast cancer patients. Our findings suggest that targeting TANs via CCL20 immunosuppressive pathway may be a novel therapeutic strategy for breast cancer treatment.
format	article
author	Louis Boafo Kwantwi Shujing Wang Wenjun Zhang Weidong Peng Zeyu Cai Youjing Sheng Han Xiao Xian Wang Qiang Wu
author_facet	Louis Boafo Kwantwi Shujing Wang Wenjun Zhang Weidong Peng Zeyu Cai Youjing Sheng Han Xiao Xian Wang Qiang Wu
author_sort	Louis Boafo Kwantwi
title	Tumor-associated neutrophils activated by tumor-derived CCL20 (C-C motif chemokine ligand 20) promote T cell immunosuppression via programmed death-ligand 1 (PD-L1) in breast cancer
title_short	Tumor-associated neutrophils activated by tumor-derived CCL20 (C-C motif chemokine ligand 20) promote T cell immunosuppression via programmed death-ligand 1 (PD-L1) in breast cancer
title_full	Tumor-associated neutrophils activated by tumor-derived CCL20 (C-C motif chemokine ligand 20) promote T cell immunosuppression via programmed death-ligand 1 (PD-L1) in breast cancer
title_fullStr	Tumor-associated neutrophils activated by tumor-derived CCL20 (C-C motif chemokine ligand 20) promote T cell immunosuppression via programmed death-ligand 1 (PD-L1) in breast cancer
title_full_unstemmed	Tumor-associated neutrophils activated by tumor-derived CCL20 (C-C motif chemokine ligand 20) promote T cell immunosuppression via programmed death-ligand 1 (PD-L1) in breast cancer
title_sort	tumor-associated neutrophils activated by tumor-derived ccl20 (c-c motif chemokine ligand 20) promote t cell immunosuppression via programmed death-ligand 1 (pd-l1) in breast cancer
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/444d247b7df34cb1aab09ee007ff3d69
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Tumor-associated neutrophils activated by tumor-derived CCL20 (C-C motif chemokine ligand 20) promote T cell immunosuppression via programmed death-ligand 1 (PD-L1) in breast cancer

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