CCR5 blockade reduces tumor growth by inducing apoptosis and impairing immunosuppression of tumor microenvironment
HE Wei
LIU Liping
ZHUO Jingwei
ZHANG Xiaodong
YANG Tong
FENG Jubin
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 apop-tosis and Caspase 8 gene expression.In a congenic mouse lung cancer model,the mice were intraperitoneally admin-istered 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 investi-gation as a candidate for cancer therapy.
Keywords：CC-chemokine receptor 5tumor microenvironmentapoptosisregulatory T cell
Publication Date：2024-05-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 1204-1210 )