中国肿瘤生物治疗杂志2026，Vol.33Issue(4)：389-399,11.DOI:10.3872/j.issn.1007-385x.2026.04.005
ILC2-AREG-Treg轴过度激活通过塑造免疫抑制微环境促进宫颈癌进展
Overactivation of the ILC2-AREG-Treg axis promotes the progression of cervical cancer by shaping an immunosuppressive microenvironment
摘要
Abstract
Objective:To investigate the role and mechanism of the group Ⅱ innate lymphoid cell(ILC2)-amphiregulin(AREG)-regulatory T(Treg)cell axis in the regulation of the immune microenvironment in cervical cancer.Methods:Tumor tissue samples were obtained from patients with stage Ⅰ-ⅡA cervical cancer(n=8)who were admitted to the First Affiliated Hospital of Xinjiang Medical University between May 2021 and May 2022.Normal cervical tissues from patients undergoing surgery for uterine fibroids served as controls(n=8).Additionally,peripheral blood samples were collected from patients with cervical cancer at all stages(n=30),with peripheral blood from healthy individuals serving as controls(n=30).The mRNA expression levels of AREG and forkhead box protein P3(Foxp3)were analyzed via the GEPIA database.Multiplex immunofluorescence and flow cytometry were performed to detect the infiltration of ILC2s and Treg cells in tissues and peripheral blood.ELISA,immunohistochemistry(IHC)and WB were carried out to verify the expression of AREG,Foxp3 and IL-10,followed by correlation analysis among ILC2s,AREG,Treg cells and IL-10.For in vitro experiments,ILC2s and peripheral blood mononuclear cell(PBMC)were isolated from cervical cancer patients and treated with recombinant human IL-33(rhIL-33),anti-IL-33 antibody(α-IL-33),recombinant human AREG(rhAREG)and anti-human AREG antibody(α-AREG),respectively.CCK-8 assay and flow cytometry were used to evaluate the effects of different concentrations of rhAREG on the proliferation and apoptosis of HeLa and SiHa cells.The concentrations of AREG and IL-10 in cell culture supernatants were measured by ELISA,and the proportion of Treg cells were determined by flow cytometry.In addition,this study also compared the differences in the levels of ILC2s,AREG,Treg cells,and IL-10 in the peripheral blood of cervical cancer patients before and after surgery.Results:The infiltration of ILC2 and expression of AREG in tissues and peripheral blood of cervical cancer patients were markedly higher than those in the normal control group.The proportion of Treg cells and expression levels of Foxp3 and IL-10 were also significantly upregulated in cervical cancer patients(P<0.05).Correlation analysis confirmed a positive correlation among ILC2s,AREG,Treg cells and IL-10.In vitro experiments showed that different concentrations of rhAREG had no significant effects on the proliferation or apoptosis of HeLa and SiHa cells(P>0.05).rhIL-33 effectively activated ILC2s and upregulated AREG secretion(P<0.01),which was reversed by α-IL-33 treatment(P<0.05).rhAREG significantly promoted Treg cell differentiation and IL-10 secretion(P<0.001),whereas α-AREG markedly reversed these biological effects(P<0.01).In addition,the levels of ILC2s,Treg cells,AREG and IL-10 in peripheral blood of cervical cancer patients were significantly decreased after surgery(P<0.000 1).Conclusion:The aberrant activation of the ILC2-AREG-Treg immunoregulatory axis may participate in cervical cancer progression by shaping an immunosuppressive tumor microenvironment.关键词
Ⅱ型固有淋巴细胞/双调蛋白/调节性T细胞/IL-10/宫颈癌/HeLa细胞/SiHa细胞Key words
group Ⅱ innate lymphoid cell(ILC2)/amphiregulin/regulatory T(Treg)cell/IL-10/cervical cancer/HeLa cell/SiHa cell分类
医药卫生引用本文复制引用
王碧辉,张玉莲,吴雨峰,丁剑冰,陈志芳..ILC2-AREG-Treg轴过度激活通过塑造免疫抑制微环境促进宫颈癌进展[J].中国肿瘤生物治疗杂志,2026,33(4):389-399,11.基金项目
国家自然科学基金(82160545,82460502) （82160545,82460502）
省部共建中亚高发病成因与防治国家重点实验室基金(SKL-HIDCA-2024-GJ2) （SKL-HIDCA-2024-GJ2）
