Cyclophosphamide abrogates the expansion of CD4+Foxp3+ regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas

Objective: Promotion of the proliferative expansion of CD4+Foxp3+ regulatory T cells (Tregs) is one of the side effects that limits the use of bleomycin (BLM) in the treatment of tumors. In this study, we examined the hypothesis that cyclophosphamide (CY), a chemotherapeutic agent with the capacity...

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Autores principales:	Ping Li, Fengyang Chen, Jingbin Zheng, Yang Yang, Yuan Li, Yifei Wang, Xin Chen
Formato:	article
Lenguaje:	EN
Publicado:	China Anti-Cancer Association 2021
Materias:	bleomycin cyclophosphamide tumor necrosis factor tregs tnfr2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0afc7b65b64c49c7b4d5bfdf3c71892c
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spelling	oai:doaj.org-article:0afc7b65b64c49c7b4d5bfdf3c71892c2021-11-30T11:27:44ZCyclophosphamide abrogates the expansion of CD4+Foxp3+ regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas2095-394110.20892/j.issn.2095-3941.2021.0027https://doaj.org/article/0afc7b65b64c49c7b4d5bfdf3c71892c2021-11-01T00:00:00Zhttp://www.cancerbiomed.org/index.php/cocr/article/view/1888https://doaj.org/toc/2095-3941Objective: Promotion of the proliferative expansion of CD4+Foxp3+ regulatory T cells (Tregs) is one of the side effects that limits the use of bleomycin (BLM) in the treatment of tumors. In this study, we examined the hypothesis that cyclophosphamide (CY), a chemotherapeutic agent with the capacity to eliminate tumor infiltrating Tregs, abrogated BLM-induced expansion of Tregs and consequently resulted in a better anti-tumor effect. Methods: The in vitro effects of BLM, with or without mafosfamide (MAF, the active metabolite of CY), on both TGF-β-induced differentiation of Tregs (iTregs), and TNF-induced expansion of naturally occurring Tregs (nTregs) were assessed. The in vivo effect of low doses of BLM and CY on tumor-infiltrating Tregs, as well as on the growth of mouse B16-F10 melanomas, was also studied. Results: In vitro treatment with BLM promoted the differentiation of iTregs, as well as TNF-induced expansion of nTregs. These effects of BLM were completely abrogated by MAF. Furthermore, in the mouse B16-F10 melanoma model, treatment with low doses of BLM increased the number of tumor-infiltrating Tregs, and this effect of BLM was also abrogated by CY. Importantly, combination therapy with low doses of BLM and CY showed synergistic anti-tumor effects. Conclusions: CY abrogated the effect of BLM on the expansion of Tregs. The combination of these 2 chemotherapeutic agents may represent a safer and more effective therapy in the treatment of cancer patients, and thus merits future clinical evaluation.Ping LiFengyang ChenJingbin ZhengYang YangYuan LiYifei WangXin ChenChina Anti-Cancer Associationarticlebleomycincyclophosphamidetumor necrosis factortregstnfr2Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Biology & Medicine, Vol 18, Iss 4, Pp 1010-1020 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bleomycin cyclophosphamide tumor necrosis factor tregs tnfr2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	bleomycin cyclophosphamide tumor necrosis factor tregs tnfr2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ping Li Fengyang Chen Jingbin Zheng Yang Yang Yuan Li Yifei Wang Xin Chen Cyclophosphamide abrogates the expansion of CD4+Foxp3+ regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas
description	Objective: Promotion of the proliferative expansion of CD4+Foxp3+ regulatory T cells (Tregs) is one of the side effects that limits the use of bleomycin (BLM) in the treatment of tumors. In this study, we examined the hypothesis that cyclophosphamide (CY), a chemotherapeutic agent with the capacity to eliminate tumor infiltrating Tregs, abrogated BLM-induced expansion of Tregs and consequently resulted in a better anti-tumor effect. Methods: The in vitro effects of BLM, with or without mafosfamide (MAF, the active metabolite of CY), on both TGF-β-induced differentiation of Tregs (iTregs), and TNF-induced expansion of naturally occurring Tregs (nTregs) were assessed. The in vivo effect of low doses of BLM and CY on tumor-infiltrating Tregs, as well as on the growth of mouse B16-F10 melanomas, was also studied. Results: In vitro treatment with BLM promoted the differentiation of iTregs, as well as TNF-induced expansion of nTregs. These effects of BLM were completely abrogated by MAF. Furthermore, in the mouse B16-F10 melanoma model, treatment with low doses of BLM increased the number of tumor-infiltrating Tregs, and this effect of BLM was also abrogated by CY. Importantly, combination therapy with low doses of BLM and CY showed synergistic anti-tumor effects. Conclusions: CY abrogated the effect of BLM on the expansion of Tregs. The combination of these 2 chemotherapeutic agents may represent a safer and more effective therapy in the treatment of cancer patients, and thus merits future clinical evaluation.
format	article
author	Ping Li Fengyang Chen Jingbin Zheng Yang Yang Yuan Li Yifei Wang Xin Chen
author_facet	Ping Li Fengyang Chen Jingbin Zheng Yang Yang Yuan Li Yifei Wang Xin Chen
author_sort	Ping Li
title	Cyclophosphamide abrogates the expansion of CD4+Foxp3+ regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas
title_short	Cyclophosphamide abrogates the expansion of CD4+Foxp3+ regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas
title_full	Cyclophosphamide abrogates the expansion of CD4+Foxp3+ regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas
title_fullStr	Cyclophosphamide abrogates the expansion of CD4+Foxp3+ regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas
title_full_unstemmed	Cyclophosphamide abrogates the expansion of CD4+Foxp3+ regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas
title_sort	cyclophosphamide abrogates the expansion of cd4+foxp3+ regulatory t cells and enhances the efficacy of bleomycin in the treatment of mouse b16-f10 melanomas
publisher	China Anti-Cancer Association
publishDate	2021
url	https://doaj.org/article/0afc7b65b64c49c7b4d5bfdf3c71892c
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Cyclophosphamide abrogates the expansion of CD4+Foxp3+ regulatory T cells and enhances the efficacy of bleomycin in the treatment of mouse B16-F10 melanomas

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