The Infiltration And Prognostic Value Of TCF1+CD8+T Cells In Small Cell Carcinoma Of The Esophagus

Background:Small cell carcinoma of the esophagus(SCCE)is characterized by low incidence,aggressiveness,and poor prognosis.TCF1+CD8+T cells have stem-cell like properties and are able to self-renew and differentiate into terminal effector T cells(TCF1-CD8T+cells)to enhance anti-tumor responses.TCF1+CD8+T cells have been shown to correlate with tumor regression and prognosis.In addition,tumors can produce immune escape by downregulating human leukocyte antigen class Ⅰ(HLA-Ⅰ).HLA-Ⅰ plays an important role in antigen presentation and is a prerequisite for CD 8+ T cell killing of tumors.The role of TCF1+CD8+T cells and HLA-Ⅰ in predicting the prognosis of patients with SCCE is still unclear.Methods:A total of 79 patients diagnosed with SCCE at Shandong University Cancer Center and Shandong Provincial Hospital Affiliated to Shandong University were selected.Information on the clinicopathological characteristics of the patients was collected,and their biopsies and surgical tissue specimens were obtained.Multiplex immunofluorescence was used for co-localization analysis of CD4,CD8,and TCF1 stained simultaneously in the tumor tissues to clarify the infiltration of TCF1+CD8+T cells,and TCF1+CD4+T cells,respectively.Patients were divided into two groups by determining the optimal cut-off value based on the time-dependent ROC.In addition,immunohistochemical staining was used to clarify the expression of HLA-Ⅰ within the tumor.The correlation between marker expression(TCF1+CD8+T cells,TCF1+CD4+T cells and HLA-Ⅰ)and clinicopathological characteristics was explored by chi-square analysis.The Kaplan-Meier curves was used to clarify OS rates,and the Log-rank test was used to compare differences in OS rates.Cox regression analysis model was used to determine independent prognostic factors associated with survival time.Result:The optimal cut-off values for TCF1+CD8+T cells and TCF1+CD8/CD8 ratio were 0.34%and 21%,respectively,and patients were divided into high and low groups using this cut-off values.The infiltration of TCF1+CD8+T cells correlated with the T stage(P=0.033).The ratio of TCF1+CD8/CD8 correlated with the T stage(P=0.002),metastasis of lymph nodes(P=0.011),and distant metastasis(P=0.013).Patients with high infiltration of TCF1+CD8+T cells had longer OS than those with low infiltration(median OS,31 vs 17 months;P=0.009;HR=0.50).Patients with high TCF1+CD8/CD8 ratio had higher OS than those with low ratio(median OS,31 vs 16 months;P<0.001,HR=0.394).The optimal cut-off values for TCF1+CD4+T cells and TCF1+CD4/CD4were 0.28%and 5%,respectively.TCF1+CD4+T cells correlated with M stage(P=0.038).Neither TCF1+CD4+T cells nor TCF1+CD4/CD4 were significantly correlated with OS.HLA-Ⅰ was defined as high and low expression groups according to immunohistochemical scoring criteria.There was no significant correlation between HLA-Ⅰ expression and clinicopathological features.Patients with high HLA-Ⅰ expression and those with low HLA-Ⅰ expression also did not show significant differences in OS(P=0.962).However,patients with high infiltration of TCF1+CD8+T cells had longer OS than those with low infiltration when they had high HLA-Ⅰ expression(median OS,32 vs 16 months;P=0.008).Multivariate analysis showed that TCF1+CD8/CD8 ratio(P=0.004)was an independent prognostic predictor.Conclusion:In patients with SCCE,TCF1+CD4+T cell and HLA-Ⅰ expression were not associated with prognosis.Both high infiltration of TCF1+CD8+T cells and high ratio of TCF1+CD8/CD8 were associated with good prognosis.TCF1+CD8+T/CD8+T is independent prognostic predictor.