Correlation Between Tumor Microenvironment-related Factors And The Efficacy And Prognosis Of Neoadjuvant Therapy For Rectal Cancer

Objective:To explore the correlation between tumor microenvironment-related factors(CD4,CD8,CTLA-4,FOXP3,PD-L1)and the efficacy and prognosis of neoadjuvant therapy for rectal cancer,and to compare the differences between two treatments[neoadjuvant chemotherapy(NAC)and neoadjuvant chemoradiotherapy(nACR)].And analyze the difference between the expression of PD-L1 in the microsatellite instability(MSI)and microsatellite Stable(MSS)of rectal cancer.Methods:1.Immunohistochemical method was used to measure the expression levels of CD4~+tumor-infiltrating lymphocytes(TILs),CD8~+TILs,FOXP3~+TILs,CTLA-4~+TILs,and PD-L1~+TILs in 109 patients with rectal cancer before and after neoadjuvant therapy,and analyze the relationship between the expression of these indicators and clinical therapeutic effect and prognosis.2.Collect the data of patients diagnosed as mismatch repair protein defect in the database of Shanxi cancer hospital.Then the MSI status of tumor was determined by fluorescence multiplex PCR technology,and the correlation between the expression level of PD-L1~+TILs and MSI was analyzed.Results:1.The CD4~+TILs,CD8~+TILs,and CTLA-4~+TILs of the resected specimens after the neoadjuvant therapy were significantly higher than those before the neoadjuvant therapy(P=0.002,P=0.001,P=0.003).After neoadjuvant therapy,the percentage of positive cells in PD-L1~+TILs decreased(P=0.001).The expression of FOXP3~+TILs was relatively stable before and after the neoadjuvant therapy.2.The patients with poorly differentiated adenocarcinoma,high CD4~+TIL,low FOXP3~+TILs and high PD-L1~+TILs before neoadjuvant therapy were more likely to have a good response to neoadjuvant therapy(P=0.007,P=0.006,P=0.001,P=0.001).The patients with high expression of CD4~+TILs,CD8~+TILs,PD-L1~+TILs and low expression of CTLA-4~+TILs and FOXP3~+TILs after neoadjuvant therapy were more likely to have a good response to neoadjuvant therapy(P=0.017,P=0.030,P=0.001,P=0.044,P=0.007).3.CD8~+TILs and FOXP3~+TILs after neoadjuvant therapy were independent prognostic factors and affected the overall survival of patients subjected to neoadjuvant therapy for rectal cancer(P=0.037,P=0.013).Moreover,there was a strong correlation between CTLA-4~+TILs and FOXP3~+TILs after neoadjuvant therapy(Pearson correlation=0.252,P=0.008).4.The percentage of CTLA-4~+TILs-positive cells was significantly higher in nACR than in NAC(P=0.000).5.The percentage of PD-L1~+TILs positive cells in MSI rectal cancer was significantly higher than that of MSS rectal cancer(P=0.003).Conclusion:1.The high expression of CD4~+TILs and CD8~+TILs suggested that neoadjuvant therapy was more likely to have a good response.The high expression of CTLA-4~+TILs and FOXP3~+TILs suggested that treatment was more likely to have a poor response.CD8~+TILs and FOXP3~+TILs after neoadjuvant therapy were independent prognostic factors and affected the overall survival of patients subjected to neoadjuvant therapy for rectal cancer.The relationship between PD-L1~+TILs and curative effect and prognosis needs to be further explored.2.The effects of NAC and nACR on tumor microenvironment may be different.3.The positive rate of PD-L1~+TILs in MSI rectal cancer is high,and PD-L1blockers may have a good respose on the treatment of MSI rectal cancer.