CMTM4 Regulates the Differentiation and Immune Effects of MDSCs in Cervical Cancer
10.13865/j.cnki.cjbmb2024.11.1271
- VernacularTitle:CMTM4调节宫颈癌髓源性抑制细胞分化和免疫效应
- Author:
Hai-Yan WANG
1
;
Jian-Hui LIU
1
;
Xiao-Ying A
1
;
Jia-Liang WANG
1
;
Qing-Fen MU
1
;
Jing ZHOU
1
;
An-Qi YANG
1
Author Information
1. 青海大学附属医院妇科,西宁810001
- Publication Type:Journal Article
- Keywords:
CKLF like MARVEL transmembrane domain containing 4 (CMTM4);
cervical cancer;
myeloid-derived suppressor cells (MDSCs) differentiation;
immune escape
- From:
Chinese Journal of Biochemistry and Molecular Biology
2024;40(12):1742-1750
- CountryChina
- Language:Chinese
-
Abstract:
The aberrant expression of CMTM4 protein has been implicated in tumorigenesis,develop-ment,and prognosis;however,its precise role and underlying mechanism in cervical cancer remain elu-sive.We aimed to investigate the expression level of CMTM4 in cervical cancer and its regulatory effect and molecular mechanism on MDSCs differentiation and immune cell function.Firstly,immunohisto-chemical (IHC) staining and Western blot analysis were employed to assess the expression level of CMTM4 in cervical cancer tumors and adjacent tissues.The results revealed a significant decrease in the expression level of CMTM4 in cervical cancer tissues compared to adjacent tissues (P<0.01) .Differenti-ation of MDSCs in tumor samples from cervical cancer patients was assessed using flow cytometry,with CD45,CD11b,and Ly6G used as markers for M-MDSCs,and CD45,CD11b,and Ly6C used as mark-ers for G-MDSCs.The percentage of M-MDSCs and G-MDSCs in the blood of cervical cancer patients was significantly higher than that observed in healthy volunteers (P<0.01) .Furthermore,flow cytometry a-nalysis demonstrated that high expression of CMTM4 increased the proportion of CD3+CD4+T cells and CD3+CD8+T cells in the blood of cervical cancer patients (P<0.01),while also promoting the activa-tion ratio of Th1 and Th17 cells (P<0.05) .Conversely,it inhibited the activation ratio of Th2 and Treg cells (P<0.05 or P<0.01) .The percentage of CD8+PD-1+T cells and CD8+PD-L1+T cells within tumor tissues was determined by flow cytometry analysis which showed that high expression levels of CMTM4 suppressed their presence within tumor tissues (P<0.05) .The in vitro studies demonstrated that overexpression of CMTM4 in HeLa cells significantly suppressed the generation of MDSCs (P<0.01),while overexpression of PD-1 in HeLa cells further enhanced the generation of MDSCs (P<0.05) .Additionally,ELISA was employed to measure the levels of Th1,Th2,Th17,and Treg cyto-kines.It was observed that CMTM4 overexpression in HeLa cells reduced IL-10 secretion by T cells (P<0.01),but increased IFN-γ and TNF-α secretion (P<0.01),both of which were reversed by PD-1 overexpression (P<0.05 or P<0.01) .In conclusion,low expression of CMTM4 in cervical cancer leads to abnormal differentiation of MDSCs and immune escape of tumors.CMTM4 influences the activation of tumor T cells by regulating the PD-1/PD-L1 pathway.Thus,CMTM4 may be a potential target for the treatment of cervical cancer.
