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

ABSTRACT: 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. 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.

SUBMITTER: Li P 

PROVIDER: S-EPMC8610150 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature