乳腺癌异常表达B7-H4对T细胞分泌细胞因子和凋亡的影响 乳腺癌异常表达B7-H4对T细胞分泌细胞因子和凋亡的影响

目的：探讨B7-H4在乳腺癌中的表达及其对外周血T细胞分泌细胞因子及增殖、凋亡的影响。方法：应用S-P免疫组化法检测B7-H4在乳腺浸润性癌、癌旁组织和纤维腺瘤的表达。流式细胞术分析B7-H4对乳腺癌患者外周血活化T细胞增殖和凋亡的作用。ELISA芯片检测T细胞培养上清液细胞因子的含量。结果：B7-H4在乳腺浸润性癌的阳性表达率为84.62%(44/52)，显著高于癌旁组织和纤维腺瘤组织（P<0.01，P<0.01 ）。体外淋巴细胞混合培养结果显示，与空白组比较，B7-H4对乳腺癌患者外周血活化T细胞的增殖指数Ki67无明显影响；但B7-H4诱导CD8+T细胞凋亡的作用强于CD4+T 细胞。B7-H4组FOXP3+T/CD4+T也高于空白组（P<0.05 ）。B7-H4组较空白组细胞培养上清液中TGF-β1、IL-17含量均显著增高（P<0.05，P<0.05）。结论：乳腺浸润性癌异常表达B7-H4。B7-H4在体外能促进CD8+T细胞凋亡、促进T细胞分泌TGF-β1 和IL-17。B7-H4在削弱乳腺癌微环境的抗肿瘤细胞免疫中发挥一定作用。

B7-H4 expression in human breast carcinoma and its role on cytokine secretion and apoptosis of peripheral blood T cells

  Objective:To explore B7-H4 expression in human invasive breast carcinomas and study the effect of recombinant human B7-H4 protein on the active peripheral blood T lymphocytes of the patients in vitro.Methods: B7-H4 expression was detected in 52 cases of breast cancer with immunohistochemistry stainingAfter the activated peripheral blood T lymphocytes of breast cancer patients were co-cultured with B7-H4,the proliferation,apoptosis and cell subtypes were tested by FCM,and the concentration of cytokines in the supernatant were detected by ELISA microarray.Results: B7-H4 was expressed in 84.62% (44/52) of invasive breast cancers,with the positive rates significantly higher than that of fibroadenomas and the adjacent tissues of breast cancers(P<0.01，P<0.01)There were no significant differences of Ki67 positive rates of T cells between B7-H4 groups and blank groups;however,B7-H4 played stronger role in promoting apoptosis of CD8+T cells than that of CD4+T cells.The rate of FOXP3+T/CD4+T cells in B7-H4 groups were higher than that of blank groups（P<0.05）.concentration of TGF-β1 and IL-17 in the supernatant of B7-H4 co-cultured T cells were significantly higher than that of blank groups(P<0.05，P<0.05) .Conclusion: B7-H4 overexpresses in invasive breast carcinomasIn vitro，B7-H4 promotes apoptosis of CD8+T cells,and the secretion of IL-17 and TGF-β1 by T cells .B7-H4 plays a role in weakening anti-tumor T cell immune response of the breast cancer microenviroment.