负性共刺激分子B7-H4在结直肠癌及其微环境中的表达及临床意义

负性共刺激分子B7-H4是新近发现的B7家族的新成员。为了检测人结直肠癌组织中肿瘤细胞及肿瘤浸润淋巴细胞(tumor-infiltrating lymphocyte,TIL)上B7-H4的表达以及分析巨噬细胞、T淋巴细胞及其亚群的浸润,进而探讨其相关临床意义,本课题采用免疫组化SP法检测98例人结直肠癌组织中肿瘤细胞及浸润淋巴细胞上B7-H4的表达以及巨噬细胞、T细胞及其亚群的浸润,统计学分析B7-H4的表达与患者临床病理参数、预后、肿瘤相关巨噬细胞(tumor-associated mac-rophage,TAM)以及CD3+T细胞、CD8+T细胞浸润程度的相关性。结果显示,结直肠癌组织中高表达B7-H4分子,而正常组织中基本不表达,并且在肿瘤细胞及浸润淋巴细胞中均检测到B7-H4的表达。统计学分析表明,浸润淋巴细胞中B7-H4的表达与患者年龄、有无淋巴结转移、是否为粘液腺癌有关(P<0.05),与患者总体生存率呈负相关(P<0.05),且B7-H4高表达组织较B7-H4低表达组织CD3+T细胞高度浸润例数显著增加(P<0.05);肠癌细胞中B7-H4的表达与患者肿瘤分期、淋巴结转移、有无远处转移以及Dukes分期有关(P<0.05)。综上所述,人结直肠癌患者的肠癌细胞及浸润淋巴细胞较正常细胞均异常表达B7-H4分子,CD3+T细胞的浸润程度与浸润淋巴细胞中B7-H4的表达呈显著相关而与肿瘤细胞上B7-H4的表达无关,而肿瘤细胞表达B7-H4与肿瘤分期、淋巴结转移、有无远处转移以及Dukes分期有关。上述结果提示肿瘤细胞表达B7-H4与浸润淋巴细胞表达B7-H4可能分别以不同机制参与了肿瘤的发生和进展,进一步分析肿瘤组织中B7-H4在不同细胞表达的生物学和临床意义具有重要的价值。

Expression and clinical significance of B7-H4 in human colorectal carcinoma and the tumor microenvironment

To detect the expression of B7-H4,a novel member of B7 superfamily,on human colon and rectal cancer(CRC) cells and tumor-infiltrating lymphocytes(TILs) and to analyze the infiltration density of macrophages and T cell subsets for the exploration of their clinical significance,we evaluated the expression of B7-H4 on tumor cells and TILs and the infiltration of macrophages and T cell subsets in 98 excised colorectal tumors by immunochemistry,then analyzed their correlations to patients’ clinical parameters and postoperative prognosis statistically.The results showed that B7-H4 was highly expressed in CRC tissuses,including tumor cells and TILs,but not or slightly in normal tissues.The B7-H4 expression on TILs was significantly correlated with patients’ age,lymph node metastasis,mucus adenocarcinoma status,inversely correlated with patients’ overall survival rate(P<0.05).The number of cases with severe CD3+T cell infiltration increased more markedly in B7-H4 high expression tissues than in low expression tissues.But the expression of B7-H4 on tumor cells was significantly correlated with tumor stage,lymph node metastasis,distant metastasis and Duke’s stage(P<0.05).In conclusion,negative costimulatory molecule B7-H4 is unusually expressed on both tumor cells and TILs in human CRC.The intensity of CD3+T cells infiltrating was significantly correlated with B7-H4 expression on TILs but not on tumor cells.The expression of B7-H4 on tumor cells was significantly correlated with tumor stage,lymph node metastasis,distant metastasis and Duky’s stage.These results suggest that B7-H4 expression on TILs and tumor cells in CRC plays different roles in the development of the cancer.In addition,it may have an important value for further analysis of biological and clinical significance of B7-H4 expression on different cells in tumor tissue.