转化生长因子-β联合CD3^(+)、CD4^(+)、CD8^(+)T细胞检测胶质母细胞瘤免疫微环境初探

A preliminary study on transforming growth factor-βcombined with CD3^(+),CD4^(+),CD8^(+)T cells in detecting the immune microenvironment of glioblastoma

目的分析胶质母细胞瘤免疫微环境中相关免疫细胞及免疫抑制因子的表达。方法纳入2020年11月至2021年4月在暨南大学附属第一医院和广东三九脑科医院行手术切除并保存完整的30例胶质瘤标本,均为胶质母细胞瘤,IDH野生型,免疫组化染色检测胶质母细胞瘤免疫微环境中T淋巴细胞(CD3^(+)、CD4^(+)、CD8^(+)T细胞)、抑制性免疫细胞[FoxP3^(+)调节性T细胞(Treg)]、免疫抑制因子[转化生长因子-β(TGF-β)]和免疫抑制信号[细胞程序性死亡蛋白配体(PDL1)]分布和表达。结果CD4^(+)T细胞在胶质母细胞瘤中占比极低;15例(50%)CD3^(+)T细胞占比>3%,CD8^(+)T细胞分布与CD3^(+)T细胞相似;仅2例(6.67%)检测到极少FoxP3^(+)Treg细胞。24例(80%)胶质母细胞瘤胞质强阳性表达TGF-β,且其表达与CD3^(+)T细胞分布存在相关性,TGF-β高表达区域未见CD3^(+)T细胞,TGF-β低表达区域CD3^(+)T细胞分布较广;无一例检测到PDL1表达。结论TGF-β蛋白在胶质母细胞瘤中呈高表达,未来针对TGF-β为靶点设计的药物或免疫疗法可能有助于胶质母细胞瘤的临床治疗。

Objective To analyze the expression of immune cells and immunosuppressive factors in the immune microenvironment of glioblastoma.Methods A total of 30 glioma specimens,all of which were glioblastoma(IDH-wildtype),were surgically removed and completely preserved in the First Affiliated Hospital of Ji'nan University and Guangdong Sanjiu Brain Hospital from November 2020 to April 2021.T lymphocytes(CD3^(+)T cells,CD4^(+)T cells,CD8^(+)T cells),suppressive immune cells[FoxP3^(+)regulatory T cell(Treg)],immunosuppressive factors[transforming growth factor-β(TGF-β)],immunosuppressive factors[programmed cell death protein ligand 1(PDL1)]in the immune microenvironment of glioblastoma were detected by immunohistochemistry.Results The proportion of CD4^(+)T cells in glioblastoma was very low.CD3^(+)T cells accounted for more than 3%in 15 cases(50%),and CD8^(+)T cells were similar to CD3^(+)T cells.Few FoxP3^(+)Treg cells were detected in only 2 cases(6.67%).The cytoplasm of 24 cases(80%)of glioblastoma showed strong positive expression of TGF-β,and its expression was correlated with the distribution of CD3^(+)T cells.No CD3^(+)T cells were found in the areas with high expression of TGF-β,and CD3^(+)T cells were widely distributed in the areas with low expression of TGF-β.PDL1 expression was non-detected.Conclusions TGF-βprotein was highly expressed in glioblastoma,and future drugs or immunotherapies designed to target TGF-βmay contribute to the clinical treatment of glioblastoma.