Effect Of Neoadjuvant Chemoradiotherapy On The Expression Of PD-1/PD-L1 In Rectal Cancer

Objective: In this study,the expression of PD-1,PD-L1 and CD8+T cells in preoperative biopsy specimens,neoadjuvant chemoradiotherapy specimens,the upper rectal specimens and the lower rectal specimens were detected by immunohistochemistry.This study investigated the expression of PD-1 and PD-L1 and the changes of CD8+T lymphocyte in rectal cancer tissues before and after neoadjuvant chemoradiotherapy,and to explore the possible influence of neoadjuvant chemoradiotherapy on immunotherapy.Method: In this study,21 patients with rectal cancer were enrolled in Shaanxi People's Hospital.Paraffin-embedded specimens were taken from the preoperative biopsy of tumor tissue(tumor tissue without neoadjuvant chemoradiotherapy),surgical excision of tumor tissue(tumor tissue with neoadjuvant chemoradiotherapy),the upper incision tissue(normal intestinal wall tissue with chemotherapy)and the lower incision tissue(normal intestinal wall with chemoradiotherapy).The expression of PD-1/PD-L1/CD8 in paraffin tissue was detected by Max Vision method.The experimental results were analysed by Chi-Square Test and Non-Parametric Test.Result:1?PD-1:(1).There are different levels of PD-1 positive expression in four types of specimens: preoperative biopsy,surgical excision,the upper incision and the lower incision.(2).The positive rate of PD-1 in rectal wall tissue without radiotherapy was33.33%,and the positive rate after radiotherapy was 14.29%.Radiotherapy could decrease the expression of PD-1 in normal rectal wall(X2=4.902,P=0.027).(3).Analysis of the difference in expression of PD-1 between tumor tissue and undercut tissue after neoadjuvant chemoradiotherapy.The expression of PD-1(42.86%)in cancer cells was higher than that in rectal intestinal tissue after radiotherapy.(14.29%)(X2=4.444,P=0.035).(4).There was no significant difference in the expression of PD-1 between tumor tissues before and after neoadjuvant chemoradiation(P=0.834).(5).The expression of PD-1 in tumor tissues increased with the increase of TNM stage after neoadjuvant chemoradiotherapy,and the difference was statistically significant(P<0.05).2?PD-L1:(1).The positive expression of PD-L1 in tumor cell was found in the preoperative biopsy and surgical resection of rectal cancer.(2).The positive expression of PD-L1 in immune cells was found in three types of specimens:resection of rectal cancer,the upper incision of surgical specimens and the lower incision of surgical specimens.(3).The positive expression of PD-L1 in different yp N stages of resected rectal cancer was different,and the difference was statistically significant(P=0.039).(4).The positiveexpression of PD-L1 in immune cells in different yp N stages of the lower incision tissues of rectal cancer specimens was different,and the difference was statisically significant(P=0.004).3?CD8:(1).CD8 positive expression of immune cells was found in four types of specimens of rectal cancer: preoperative biopsy,surgical resection,the upper incision and the lower incision.(2).The difference of CD8 expression between preoperative biopsy tissue and surgical resection tissue,surgical resection tissue and the lower incision tissue of surgical specimens was analyzed,and the difference was statisically significant(P=0.001,P=0.001),neoadjuvant chemoradiotherapy can significantly increase the expression of CD8 in cancer tissues,and the expression of CD8 in cancer tissues is higher than that in normal tissues after chemoradiotherapy.Radiotherapy had no significant effect on the expression of CD8 in normal intestinal wall tissue.Conclusion:1.The expression of PD-1/tumor cell PD-L 1 may be related to the stage of the tumor.With the increase of stage,the expression of PD-1 increases and the expression of PD-L1 decreases.2.Radiotherapy had no significant effect on the expression of CD8+ T cells in the normal rectal wall,but decreased the expression of PD-1,which decreased the possibility of programmed cell death of lymphocytes through the PD-1-PD-L1 pathway.3.Neoadjuvant chemoradiotherapy can increase the expression of CD8+ T cells in rectal tumor tissues,and the same time increase the expression of PD-1 in lymphocytes in tumor tissues,resulting in tumor infiltrating lymphocytes may be more readily programm-ed death by the pathway of PD-1-PD-L1.