肿瘤微环境相关因子与直肠癌新辅助化疗效果及微卫星稳定状况的关系

Relationship between tumor microenvironment related factors and efficacy of neoadjuvant chemotherapy for rectal cancer and microsatellite stability

目的观察新辅助化疗(NAC)前后直肠癌患者肿瘤微环境内CD4、CD8、细胞毒性T淋巴细胞相关抗原-4(CTLA-4)、叉头框蛋白P3(FOXP3)、程序性死亡受体配体1(PD-L1)的表达水平,分析直肠癌患者临床特征、免疫标志物表达情况与肿瘤病理反应的关系以及PD-L1^+TIL的表达与微卫星不稳定(MSI)状况的关系。方法选取90例直肠癌患者,采用免疫组化法检测NAC前后患者CD4^+TIL、CD8^+TIL、CTLA-4^+TIL、FOXP3^+TIL和PD-L1^+TIL的表达水平,采用荧光多重聚合酶链反应检测MSI状况,分析MSI与微卫星稳定(MSS)状态下PD-L1^+TIL表达的差异性。结果 NAC后,直肠癌患者CD4^+TIL、CD8^+TIL、CTLA-4^+TIL的表达水平均明显高于NAC前,PD-L1^+TIL的表达水平明显低于NAC前(P﹤0.01)。NAC前后,患者的FOXP3^+TIL的表达水平比较,差异无统计学意义(P﹥0.05)。90例直肠癌患者中,MSI患者40例,MSS患者50例。MSI患者中PD-L1^+TIL的阳性细胞比例明显高于MSS患者(P﹤0.01)。结论 MSI直肠癌患者PD-L1^+TIL的阳性率高,PD-L1阻断剂对MSI直肠癌患者的疗效可能更好。

Objective To observe the expression of CD4,CD8,cytotoxic T lymphocyte associated antigen-4(CTLA-4),forkhead box P3(FOXP3),programmed cell death 1 ligand 1(PD-L1)before and after neoadjuvant chemotherapy(NAC),to analyze the relationship among patients’clinical characteristics,expression immunological markers and tumor’s pathological response,and the association with PD-L1+tumor infiltrating lymphocyte(TIL)expression and microsatellite instability(MSI)status.Method A total of 90 patients with rectal cancer were included in the analysis,immunohistochemical staining was used to detect the expression of CD4+TIL,CD8+TIL,CTLA-4+TIL and FOXP3+TIL,as well as PD-L1+TIL in these patients before and after NAC.The MSI status of patients was detected by fluorescent multiplex polymerase chain reaction,so as to determine the differential expression of PD-L1+TIL in MSI or microsatellite stability(MSS).Result The expression of CD4+TIL,CD8+TIL,CTLA-4+TIL in rectal cancer patients were increased after NAC compared to before NAC,while the expression of PD-L1+TIL was suppressed after NAC(P<0.01).There was no significant difference in the expression of FOXP3+TIL in patients before and after NAC(P>0.05).Among the 90 patients with rectal cancer,40 were MSI patients and 50 were MSS patients.The proportion of PD-L1+TIL positive cells in MSI patients was significantly higher than that in MSS patients(P<0.01).Conclusion The positive rate of PD-L1+TIL is elevated in patients with rectal cancer with MSI,with possibly better efficacy for PD-L1 blocker in rectal cancer with MSI.