Epression And Significance Of Tumor Infiltrating T-lymphocyte Subsets In Patients With Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma Received Preoperative Neoadjuvant Chemotherapy And Immunotherapy

Objective:To investigate the expression of Tumor Infiltrating T-lymphocyte Subsets in patients with Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma(ESCC)after neoadjuvant chemotherapy combined with immunotherapy(Sintilimab),and to explore its correlation with clinicopathological features of ESCC,in order to provide a theoretical basis for the application of chemotherapy combined with immunotherapy in preoperative neoadjuvant therapy for Locally Advanced ESCC.Methods:The expression of CD3+,CD4+,CD8+and FOXP3+T-lymphocytes in tumor tissues were detected by the immunohistochemical methods in 31 patients with locally advanced ESCC who received preoperative neoadjuvant chemotherapy combined with immunotherapy(Group NAC+I)in the Thoracic Surgery Department,Affiliated Hospital of North Sichuan Medical College from January 2020 to October 2021,compared with 31 patients with preoperative neoadjuvant chemotherapy(Group NAC),and 33 patients received surgery alone(Group S)in the same time.The expression differences of CD3+,CD4+,CD8+ and FOXP3+T-lymphocytes in tumor tissues of the three patient groups were detected by the immunohistochemical method.Statistical methods were used to compare the differences of tumor infiltrating T-lymphocyte subsets in patients with different treatment plans,and analyze the influence of neoadjuvant chemotherapy combined with immunotherapy on the expression levels of tumor local CD3+,CD4+,CD8+ and FOXP3+ T-lymphocytes and its correlation with clinicopathological parameters.Results:1.PCR and MPR in Group NAC+I were higher than those in Group NAC(32.3%vs.9.7%;48.4%vs.12.9%),and the differences were statistically significant(P<0.05).Compared with NAC,the down-staging of ypT stage was more significant after preoperative neoadjuvant chemotherapy combined with immunotherapy(P<0.05).2.The proportion of CD3+TILs positive cells in Group NAC+I was higher than that in Group NAC and Group S(P<0.05);there was no significant difference in the proportion of CD4+TILs positive cells among the three patient groups(P>0.05).The proportion of CD8+TILs positive cells in Group NAC+I was significantly higher than that in Group NAC and Group S(P<0.05);there was no statistical meaning in the difference of the proportion of FOXP3+TILs positive cells in the two groups of neoadjuvant therapy patients(P>0.05),while the proportion of FOXP3+TILs positive cells in the neoadjuvant group was significantly higher than that in Group S(P<0.05).3.After neoadjuvant chemotherapy combined with immunotherapy,the expression of CD3+,CD8+ and FOXP3+TILs was significantly increased(P<0.05),and there was no statistical difference in the expression of CD4+TILs among the three patient groups(P>0.05).4.There was no significant correlation between tumor regression degree and age,gender,clinical T stage,clinical N stage and FOXP3+TILs expression level(P>0.05),while tumor regression degree was significantly correlated with vascular/nerve invasion,neoadjuvant therapy,expression levels of CD3+TILs,CD4+TILs and CD8+TILs(P<0.05).Vascular/nerve invasion was significantly lower in the response group(P<0.05);tumor regression degree was significantly higher in Group NAC+I(73.9%vs 26.1%,P<0.05);tumor regression was more evident in patients with high expression of CD3+TILs,CD4+TILs and CD8+TILs(P<0.05).5.After neoadjuvant chemotherapy combined with immunotherapy,the high expression of CD3+TILs and CD8+TILs in tumor tissues was related to PCR,MPR and tumor infiltrating depth(P<0.05),but had no significant correlation with age,gender,tumor location,lymph node metastasis and ypTNM stage(P>0.05).The high expression of FOXP3+TILs was related to PCR;there was no significant correlation between the expression level of CD4+TILs and age,gender,tumor location,PCR,MPR,tumor infiltrating depth,lymph node metastasis and ypTNM stage(P>0.05).The high expression of CD8+TILs in the surgery alone was related to the tumor infiltrating depth,lymph node metastasis and pTNM stage(P<0.05),but the expression levels of CD3+TILs,CD4+TILs and FOXP3+TILs were not significantly correlated with age,gender,tumor location,tumor infiltrating depth,lymph node metastasis and pTNM stage(P>0.05).Conclusion:1.Compared with neoadjuvant chemotherapy,neoadjuvant chemotherapy combined with immunotherapy had a higher PCR rate,MPR rate and more obvious tumor down-staging.2.After neoadjuvant chemotherapy combined with immunotherapy,the expression levels of CD3+TILs,CD8+TILs and FOXP3+TILs in tumor tissues of ESCC increased significantly,while the expression level of CD4+TILs did not change significantly.3.Compared with neoadjuvant chemotherapy,tumor regression degree(TRG1-2 Grade)was more evident in patients treated with combined immunotherapy;vascular/nerve invasion,low expression of CD3+TILs,CD4+TILs,and CD8+TILs may signal poor regression(TRG3-5 Grade)after neoadjuvant therapy.The high expression of CD8+TILs in patients with surgery alone was related to the tumor infiltrating depth,lymph node metastasis and pTNM stage,and the high expression of CD8+TILs could be used as an auxiliary predictor of good prognosis.The high expression of CD3+TILs and CD8+TILs in neoadjuvant chemotherapy combined with immunotherapy was related to PCR,MPR and tumor infiltrating depth and patients with high expression of CD3+TILs and CD8+TILs had better short-term effects.In this study,the high expression of FOXP3+TILs after chemotherapy combined with immunotherapy was related to PCR,and the reasons for this need to be further explored.