MDSCs在食管鳞癌术后患者免疫微环境中的表达及与CD8^(+)T细胞的关系

The expression of MDSCs in the immune microenvironment of esophageal squamous cell carcinoma patients and their relationship with CD8^(+)T cells

目的探讨髓源性抑制细胞(MDSCs)在食管鳞癌术后患者免疫微环境中的表达及与CD8^(+)T细胞的关系。方法选取2020年1月—2021年10月中国人民解放军西部战区总医院肿瘤科诊治食管鳞癌患者103例,根据预后情况分为无进展组、病情进展组,均在治疗前采用流式细胞仪测定MDSCs占单个核细胞(PBMC)百分比及CD8^(+)T细胞比率。比较不同病理特征患者MDSCs比率和CD8^(+)T细胞比率,分析MDSCs比率与CD8^(+)T细胞比率相关性及二者与患者无进展生存率的关系。绘制Kaplan-Meier生存曲线比较不同MDSCs比率和CD8^(+)T细胞患者无进展生存率。结果103例患者随访过程失访5例,病情进展46例,无进展52例。浸润深度T3/T4、淋巴结转移患者MDSCs比率高于浸润深度T1/T2、无淋巴结转移者,CD8^(+)T细胞比率低于浸润深度T1/T2、无淋巴结转移者(t/P=2.570/0.012,2.445/0.016,2.954/0.004,2.578/0.011);随着分化程度降低,MDSCs比率呈升高趋势,CD8^(+)T细胞呈降低趋势(F/P=5.993/0.004,6.842/0.002);MDSCs比率与CD8^(+)T细胞比率呈负相关(r/P=-0.654/<0.001);病情进展组浸润深度、淋巴结转移、CEA、CA199、MDSCs比率高于无进展组,分化程度、CD8^(+)T细胞比率低于无进展组,差异有统计学意义(P<0.05)。Cox回归模型分析发现,调整浸润深度、淋巴结转移、分化程度、CEA、CA199混杂因素后MDSCs比率高仍为患者病情进展独立危险因素[HR(95%CI)=4.011(2.325~6.921)],CD8^(+)T细胞比率高仍为独立保护因素[HR(95%CI)=0.267(0.178~0.402)];不同MDSCs比率、CD8^(+)T细胞比率患者无进展生存率比较,差异有统计学意义(χ^(2)/P=8.911/0.003、15.340/<0.001)。结论食管鳞癌患者免疫微环境中MDSCs比率升高可能通过抑制CD8^(+)T细胞活性而增强食管鳞癌细胞的免疫逃逸能力,从而促进食管鳞癌的发生发展。

Objective To investigate the expression of myeloid Sexual inhibition cells(MDSCs)in the immune microenvironment of patients with esophageal squamous cell carcinoma and its relationship with CD8^(+)T cells.Methods From January 2020 to October 2021,103 patients with esophageal squamous cell carcinoma diagnosed and treated by the Department of Oncology of the General Hospital of the Western Theater Command were selected.According to the prognosis,they were divided into non progression group and progression group.Before treatment,the percentage of MDSCs in mononuclear cells(PBMC)and the ratio of CD8^(+)T cells were measured by flow cytometry.Compare the MDSCs ratio and CD8^(+)T cell ratio in patients with different pathological characteristics,analyze the correlation between MDSCs ratio and CD8^(+)T cell ratio,and the relationship between the two and the progression free survival rate of patients.Draw Kaplan Meier survival curves to compare the progression free survival rate of patients with different MDSCs ratios and CD8^(+)T cells.Results During the follow-up of 103 patients,5 cases were lost,46 cases progressed,and 52 cases did not progress.Patients with infiltration depth T3/T4,lymph node metastasis had a higher MDSCs ratio than those with infiltration depth T1/T2,and no lymph node metastasis.The CD8^(+)T cell ratio was lower than those with infiltration depth T1/T2,and no lymph node metastasis(t/P=2.570/0.012,2.445/0.016,2.954/0.004,2.578/0.011);As the degree of differentiation decreases,the ratio of MDSCs shows an increasing trend,while CD8^(+)T cells show a decreasing trend(F/P=5.993/0.004,6.842/0.002);The ratio of MDSCs is negatively correlated with the ratio of CD8^(+)T cells(r/P=-0.654/<0.001);The progression group had higher rates of infiltration depth,lymph node metastasis,CEA,CA199,and MDSCs compared to the non-progression group,while the differentiation degree and CD8^(+)T cell ratio were lower than those of the non-progression group,with statistically significant differences(P<0.05).Cox regression model analysis found that adjusting for infiltration depth,lymph node metastasis,differentiation degree,CEA After confounding with CA199,the ratio of MDSCs and CD8^(+)T cells remained independent influencing factors for patient progression[HR(95%CI)=4.011(2.325-6.921),0.267(0.178-0.402)];Comparison of progression free survival rates among patients with different MDSCs ratios and CD8^(+)T cell ratios,with statistically significant differences(χ^(2)/P=8.911/0.003,15.340/<0.001).Conclusion The increased proportion of MDSCs in the immune microenvironment of esophageal squamous cell carcinoma patients may enhance the immune escape ability of esophageal squamous cell carcinoma cells by inhibiting CD8^(+)T cell activity,thereby promoting the occurrence and development of esophageal squamous cell carcinoma.