Type I Interferon Promotes Antitumor T Cell Response in CRPC by Regulating MDSC

Background: Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among prostate cancer patients. Here, our aim was to ascertain the immune regulatory mechanisms involved in CRPC development and identify potential immunotherapies against CRPC. Methods: A CRPC model was...

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Autores principales:	Lilv Fan, Guiliang Xu, Jingjing Cao, Min Li, Huihui Zhang, Fanlin Li, Xinyue Qi, Xiaoqing Zhang, Zeyu Li, Ping Han, Xuanming Yang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	IFNα prostate cancer G-MDSC immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/fd436a2d1e8b4d2a9fc27ac955ff189d
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spelling	oai:doaj.org-article:fd436a2d1e8b4d2a9fc27ac955ff189d2021-11-11T15:35:40ZType I Interferon Promotes Antitumor T Cell Response in CRPC by Regulating MDSC10.3390/cancers132155742072-6694https://doaj.org/article/fd436a2d1e8b4d2a9fc27ac955ff189d2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5574https://doaj.org/toc/2072-6694Background: Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among prostate cancer patients. Here, our aim was to ascertain the immune regulatory mechanisms involved in CRPC development and identify potential immunotherapies against CRPC. Methods: A CRPC model was established using Myc-CaP cells in immune-competent FVB mice following castration. The immune cell profile of the tumor microenvironment (TME) was analyzed during CRPC development. Different immunotherapies were screened in the CRPC tumor model, and their efficacies and underlying mechanisms were investigated in vitro and in vivo. Results: During CRPC development, the proportion of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the TME increased. Among the immunotherapies tested, IFNα was more effective than anti-PD-L1, anti-CTLA-4, anti-4-1BB, IL-2, and IL-9 in reducing Myc-CaP CRPC tumor growth. IFNα reduced the number of G-MDSCs both in vitro during differentiation and in vivo in CRPC mice. Furthermore, IFNα reduced the suppressive function of G-MDSCs on T cell proliferation and activation. Conclusion: G-MDSCs are crucial to effective immunotherapy against CRPC. Treatment with IFNα presents a promising therapeutic strategy against CRPC. Besides the direct inhibition of tumor growth and the promotion of T cell priming, IFNα reduces the number and the suppressive function of G-MDSCs and restores T cell activation.Lilv FanGuiliang XuJingjing CaoMin LiHuihui ZhangFanlin LiXinyue QiXiaoqing ZhangZeyu LiPing HanXuanming YangMDPI AGarticleIFNαprostate cancerG-MDSCimmunotherapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5574, p 5574 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	IFNα prostate cancer G-MDSC immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	IFNα prostate cancer G-MDSC immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lilv Fan Guiliang Xu Jingjing Cao Min Li Huihui Zhang Fanlin Li Xinyue Qi Xiaoqing Zhang Zeyu Li Ping Han Xuanming Yang Type I Interferon Promotes Antitumor T Cell Response in CRPC by Regulating MDSC
description	Background: Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among prostate cancer patients. Here, our aim was to ascertain the immune regulatory mechanisms involved in CRPC development and identify potential immunotherapies against CRPC. Methods: A CRPC model was established using Myc-CaP cells in immune-competent FVB mice following castration. The immune cell profile of the tumor microenvironment (TME) was analyzed during CRPC development. Different immunotherapies were screened in the CRPC tumor model, and their efficacies and underlying mechanisms were investigated in vitro and in vivo. Results: During CRPC development, the proportion of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the TME increased. Among the immunotherapies tested, IFNα was more effective than anti-PD-L1, anti-CTLA-4, anti-4-1BB, IL-2, and IL-9 in reducing Myc-CaP CRPC tumor growth. IFNα reduced the number of G-MDSCs both in vitro during differentiation and in vivo in CRPC mice. Furthermore, IFNα reduced the suppressive function of G-MDSCs on T cell proliferation and activation. Conclusion: G-MDSCs are crucial to effective immunotherapy against CRPC. Treatment with IFNα presents a promising therapeutic strategy against CRPC. Besides the direct inhibition of tumor growth and the promotion of T cell priming, IFNα reduces the number and the suppressive function of G-MDSCs and restores T cell activation.
format	article
author	Lilv Fan Guiliang Xu Jingjing Cao Min Li Huihui Zhang Fanlin Li Xinyue Qi Xiaoqing Zhang Zeyu Li Ping Han Xuanming Yang
author_facet	Lilv Fan Guiliang Xu Jingjing Cao Min Li Huihui Zhang Fanlin Li Xinyue Qi Xiaoqing Zhang Zeyu Li Ping Han Xuanming Yang
author_sort	Lilv Fan
title	Type I Interferon Promotes Antitumor T Cell Response in CRPC by Regulating MDSC
title_short	Type I Interferon Promotes Antitumor T Cell Response in CRPC by Regulating MDSC
title_full	Type I Interferon Promotes Antitumor T Cell Response in CRPC by Regulating MDSC
title_fullStr	Type I Interferon Promotes Antitumor T Cell Response in CRPC by Regulating MDSC
title_full_unstemmed	Type I Interferon Promotes Antitumor T Cell Response in CRPC by Regulating MDSC
title_sort	type i interferon promotes antitumor t cell response in crpc by regulating mdsc
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fd436a2d1e8b4d2a9fc27ac955ff189d
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Type I Interferon Promotes Antitumor T Cell Response in CRPC by Regulating MDSC

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