Anti-Tumor Necrosis Factor Receptor 2 Antibody Combined With Anti-PD-L1 Therapy Exerts Robust Antitumor Effects in Breast Cancer

Breast cancer is a leading type of malignant tumor in women; however, the immunotherapy in breast cancer is still underappreciated. In this study, we demonstrated that tumor necrosis factor receptor 2 (TNFR2) is highly expressed in both breast tumor tissue and tumor-infiltrating immunosuppressive CD...

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Autores principales:	Qiang Fu, Qian Shen, Jin Tong, Liu Huang, Yi Cheng, Wei Zhong
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	TNFR2 breast cancer TNFR2 antagonist anti-PD-L1 therapy exert robust anti-tumor Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e1efb576d3b34b5292cfa5d81a039b9a
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spelling	oai:doaj.org-article:e1efb576d3b34b5292cfa5d81a039b9a2021-12-01T01:22:28ZAnti-Tumor Necrosis Factor Receptor 2 Antibody Combined With Anti-PD-L1 Therapy Exerts Robust Antitumor Effects in Breast Cancer2296-634X10.3389/fcell.2021.720472https://doaj.org/article/e1efb576d3b34b5292cfa5d81a039b9a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.720472/fullhttps://doaj.org/toc/2296-634XBreast cancer is a leading type of malignant tumor in women; however, the immunotherapy in breast cancer is still underappreciated. In this study, we demonstrated that tumor necrosis factor receptor 2 (TNFR2) is highly expressed in both breast tumor tissue and tumor-infiltrating immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs). We found that TNFR2 antagonistic antibody reduced Foxp3 expression and the proliferation of Tregs and impaired the inhibitory effect of Tregs on CD4+CD25– effector T (Teff) cells in a dose-dependent manner. The treatment of anti-TNFR2 antibody not only inhibited the proliferation of breast tumor cells in vitro but also suppressed the tumorigenesis of murine mammary carcinoma 4T1 cells in vivo. Mice recovered from tumor growth also developed 4T1-specific immunity. Furthermore, we demonstrated that anti-TNFR2 antibody in combination with anti-PD-L1 exhibited augmented antitumor effects than monotherapy. Anti-TNFR2 treatment also tended to increase the expression of proinflammatory cytokines in tumor tissues. In conclusion, our study suggests that TNFR2 antagonist could potentially offer a clinical benefit as a single agent or in combination with immune checkpoint blockade treatment for breast cancer immunotherapy.Qiang FuQian ShenJin TongLiu HuangYi ChengWei ZhongFrontiers Media S.A.articleTNFR2breast cancerTNFR2 antagonistanti-PD-L1 therapyexert robust anti-tumorBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TNFR2 breast cancer TNFR2 antagonist anti-PD-L1 therapy exert robust anti-tumor Biology (General) QH301-705.5
spellingShingle	TNFR2 breast cancer TNFR2 antagonist anti-PD-L1 therapy exert robust anti-tumor Biology (General) QH301-705.5 Qiang Fu Qian Shen Jin Tong Liu Huang Yi Cheng Wei Zhong Anti-Tumor Necrosis Factor Receptor 2 Antibody Combined With Anti-PD-L1 Therapy Exerts Robust Antitumor Effects in Breast Cancer
description	Breast cancer is a leading type of malignant tumor in women; however, the immunotherapy in breast cancer is still underappreciated. In this study, we demonstrated that tumor necrosis factor receptor 2 (TNFR2) is highly expressed in both breast tumor tissue and tumor-infiltrating immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs). We found that TNFR2 antagonistic antibody reduced Foxp3 expression and the proliferation of Tregs and impaired the inhibitory effect of Tregs on CD4+CD25– effector T (Teff) cells in a dose-dependent manner. The treatment of anti-TNFR2 antibody not only inhibited the proliferation of breast tumor cells in vitro but also suppressed the tumorigenesis of murine mammary carcinoma 4T1 cells in vivo. Mice recovered from tumor growth also developed 4T1-specific immunity. Furthermore, we demonstrated that anti-TNFR2 antibody in combination with anti-PD-L1 exhibited augmented antitumor effects than monotherapy. Anti-TNFR2 treatment also tended to increase the expression of proinflammatory cytokines in tumor tissues. In conclusion, our study suggests that TNFR2 antagonist could potentially offer a clinical benefit as a single agent or in combination with immune checkpoint blockade treatment for breast cancer immunotherapy.
format	article
author	Qiang Fu Qian Shen Jin Tong Liu Huang Yi Cheng Wei Zhong
author_facet	Qiang Fu Qian Shen Jin Tong Liu Huang Yi Cheng Wei Zhong
author_sort	Qiang Fu
title	Anti-Tumor Necrosis Factor Receptor 2 Antibody Combined With Anti-PD-L1 Therapy Exerts Robust Antitumor Effects in Breast Cancer
title_short	Anti-Tumor Necrosis Factor Receptor 2 Antibody Combined With Anti-PD-L1 Therapy Exerts Robust Antitumor Effects in Breast Cancer
title_full	Anti-Tumor Necrosis Factor Receptor 2 Antibody Combined With Anti-PD-L1 Therapy Exerts Robust Antitumor Effects in Breast Cancer
title_fullStr	Anti-Tumor Necrosis Factor Receptor 2 Antibody Combined With Anti-PD-L1 Therapy Exerts Robust Antitumor Effects in Breast Cancer
title_full_unstemmed	Anti-Tumor Necrosis Factor Receptor 2 Antibody Combined With Anti-PD-L1 Therapy Exerts Robust Antitumor Effects in Breast Cancer
title_sort	anti-tumor necrosis factor receptor 2 antibody combined with anti-pd-l1 therapy exerts robust antitumor effects in breast cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e1efb576d3b34b5292cfa5d81a039b9a
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Anti-Tumor Necrosis Factor Receptor 2 Antibody Combined With Anti-PD-L1 Therapy Exerts Robust Antitumor Effects in Breast Cancer

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