Analysis Of Related Factors And Prognosis Of PD-L1 Expression In Rectal Cancer

Background:Programmed death ligand-1 (PD-L1) and programmed death receptor-1 (PD-1) are a pair of immune co inhibitory molecules.The expression of PD-L1 in tumor cells can bind to PD-1 binding on the surface of T cells,inhibit the function of T cells,leading to the occurrence of immune escape of tumor cells.Therefore, blocking PD-L1 signal pathways become a new strategy of tumor immunotherapy, PD-L1 antibody has made significant clinical effect in melanoma, non small cell lung cancer and many other kinds of tumors, but rectal cancer, the reason is still not clear.Studies have shown that TIL may promote melanoma cell PD-L1 expression, leading to immune escape, which explains why the PD-1 pathway blocker achieved remarkable curative effect in the treatment of melanoma.The relationship between the expression of PD-L1 and the infiltration of TIL in rectal cancer has not been reported. In addition,the influence of PD-L1 on the prognosis of rectal cancer is controversial.Objectives:Using the technique of tissue microarray and the methods of immunohistochemical, to test the expression of PD-L1 and infiltration situation of TIL in tissue of rectal cancer. To discuss the work situation of PD-1/PD-L1 pathway in immune tolerance of rectal cancer and the potential applying value of PD-L1 blockers in curing rectal cancer; Analysis the relationship of expression of PD-L1 and the prognosis of rectal cancer patients, to discuss the clinical value of PD-L1 as marker of prognosis.Methods:Our study is a retrospective study,97 patients operated in General Surgery Department of PLA General Hospital were included, we use electronic medical record system to collect data; 2) We use telephone follow-up to collect materials of clinical pathology; 3) We made tissue microarray from tumor tissue of patients, serial section was done to get three slices, one slice was deal with HE staining and the other two were deal with methods of immune histochemical to test the expression of PD-L1 and molecule CD3 on the surface of TIL; 4) We used SPSS 17.0 to do data analysis, Statistical methods used were Fisher's exact test, Logistic regression analysis, Kaplan and Meier curves, the log-rank test and COX survival analysis.etc.Results:1) The positive rate of PD-L1 expression of tumor tissue of patients was 43.3%; Fisher's exact test was used to test the relationship between varying degrees of infiltration situation of TIL and PD-L1 expression(P<0.05).2) The single factor analysis of x2 showed that the PD-L1 expression of rectal cancer cell was related with tumor differentiation degree and stage of TNM(P<0.05), but not related with age, sex,tumor location, depth of invasion, the situation of lymph node metastasis and the situation of distant metastasis(P>0.05); The result of Logistic regression analysis after infiltration situation of TIL was added showed that infiltration situation of TIL had great impact on PD-L1 expression,OR value was 1.99 (95%CI:1.123-3.523;P=0.018); Tumor differe-ntiation degree and TNM stage were not independent factors that influence PD-L1 expression.3) The median survival time of 97 patients was 62.6 months(6-71.7 months), the five-year survival rate was 71.1%; The result of Kaplan and Meier curves and the log-rank test showed there was no significant difference between PD-L1 positive patients and PD-L1 negative patients.(P=0.165).4) The result of COX survival analysis showed that the HR value of PD-L1 after correction was 2.239 (95% CI:0.952-5.262;P=0.067); The HR value of TIL after correction was 0.390 (95% CI: 0.232-0.670;P=0.001); The HR value of tumor differentiation after correction was 1.945(95% CI:1.130-3.369;P=0.016); The HR value of TNM stage after correction was 1.821 (95% CI:1.159-2.869;P=0.009); PD-L1 expression has no impact on prognosis; TIL was a strong factor to prolong lifetime of patients;Low degree of tumor differe-ntiation and later period of TNM stage negative factor to prolong lifetime of patients.Conclusions:1) There was a significant relationship between PD-L1 expression and the infiltration situation of TIL, which indicated that PD-1/PD-L1 pathway as some kind mechanism of adaptive immune rejection may play an important role in immune escape of rectal cancer; 2) Antagonists of PD-1/PD-L1 pathway was theoretically effective in curing rectal cancer, but because of low positive rate of PD-L1, low degree of infiltration situation of TIL we need to develop more effective predictable marker to screen Sensitive patients; 3) Tumor related PD-L1 had no relationship with prognosis of rectal patients, TIL was favourable factor for prognosis, low degree of tumor differentiation and later stage of TNM were adverse factor for prognosis.