关键词: CC趋化因子受体5, 肿瘤微环境, 凋亡, 调节性T细胞

Abstract:

Objective The present study aimed to explore the effects of CC?chemokine receptor 5 antagonism on tumor growth and immune microenvironment. Methods Cell Counting Kit?8 was used to detect in vitro anti?proliferation activity of maraviroc， a selective CC?chemokine receptor 5 inhibitor， on Lewis cells， a mouse lung adenocarcinoma cell strain. Flow cytometry and real?time quantitative PCR were respectively used to detect cell apoptosis and Caspase 8 gene expression. In a congenic mouse lung cancer model， the mice were intraperitoneally administered with maraviroc or vehicle. Tumor sizes were measured and tumor infiltrating CD4⁺， CD8⁺ and Foxp3⁺ cells were determined by immunofluorescent staining. Results Our results showed that maraviroc could inhibit the growth of Lewis cancer cells not only in vitro but also in vivo. This in?vitro inhibition was presumably attributable to apoptosis induction by the enhancement of Caspase 8 gene expression after maraviroc blockade. Additionally， more CD4⁺ and CD8⁺ cells but less Foxp3⁺ cells were detected in tumor mass from the mice administered with maraviroc. Conclusions Taken together， it can be speculated that CCR5 blockade may inhibit the growth of Lewis cells by inducing cell apoptosis and impairing the immunosuppressive tumor microenvironment. It is worthy of further investigation as a candidate for cancer therapy

Key words: CC?chemokine receptor 5, tumor microenvironment, apoptosis, regulatory T cell