Relationship Among PD-L1,Clinicopathological Features And Prognosis Of Colorectal Cancer Patients

Objective:The purpose of this study is to explore the relationship among tumor cells PD-L1 expression,tumor infiltrating immune cells PD-L1 expression,immune cells infiltrating level,the clinicopathological features of colorectal cancer and the prognosis.Methods:Follow up 153 patients diagnosed with colorectal cancer treated in Peking Union Medical College Hospital from February 2011 to December 2015.Get Paraffin pathological wax blocks,make pathological sections.Perform PD-L1 immunohistochemical staining.Chi-square test to analyze the relationship among PD-L1 expression,immune cells infiltrating level andclinicopathological features.Kaplan-Meier to draw the survival curves.Log-rank test to compare the differences among groups.We aim to study the relationship between PD-L1 expression and DFS(Stage Ⅰ-Ⅲ)or PFS(Stage IV)in patients with colorectal cancer.Results:1.There were 153 colorectal patients,including 77 men,76 women.Median age was 63 years old(26-89 years).There were 10(6.5%)stage I patients,67(43.8%)Stage II patients,38(24.8%)stage III patients and 38(24.8%)stage IV patients.There were 77 pMMR patients and 28 dMMR patients of stage I-III.2.There were 78 cases(51%)of the positive tumor cells PD-L1 expression(TC+)and 64 cases(41.8%)of the positive tumor infiltrating immune cells PD-L1(TIC+).The tumor cells PD-L1 expression may be related to the tumor infiltrating immune cells PD-L1 expression(p=0.001).3.The positive rates of tumor cells PD-L1 expression in stage Ⅰ,Ⅱ,Ⅲand IV were 40%,28.4%,55.3%,89.5%,respectively,and the positive rates of tumor infiltrating immune cells PD-L1 expression were 20%,32.8%,34.2%,71%,respectively.The positive rate of PD-L1 expression in tumor cells and tumor infiltrating immune cells got higher with the increase of stages(TC+P<0.05;TIC+ P<0.01).The positive rate of tumor infiltrating immune cells PD-L1 expression in stage IV(71.1%)was higher than that in stage I-III(32.2%)(P<0.01).4.The positive rate of tumor cells PD-L1 expression in the right half colon(38.9%;37/95)was lower than that in left half colon(71.4%;40/56)(P<0.01).5.For stage I-IV CRC patients,the positive rate of tumor infiltrating immune cells PD-L1(5/26,19.2%)with low immune cells infiltrating level was lower than that with high immune cells infiltrating level(59/127,46.5%).6.For dMMR and pMMR patients of stage Ⅰ-Ⅲ,the positive rates of PD-L1 expression in tumor cells were 35.7%(10/28)and 35.1%(p=0.951),respectively.The positive rates of PD-L1 expression in tumor infiltrating immune cells were 53.6%(15/28)and 20.8%(16/77)respectively(P<0.01),respectively.7.For stage I-III pMMR patients,the negative group and positive group of PD-L1 expression in tumor cells did not reach the median DFS and HR(negative/positive)was 0.407(95%CI 0.17-0.99,p=0.047).For stage I-III dMMR patients,the high immune cells infiltrating level did not reach the median DFS and the median DFS of the low level group was 8.9 months,HR(low/high)=6.331(95%CI 1.406-28.508,p=0.016).8.For stage IV patients,the median PFS in the tumor cells PD-L1 positive group(7.1 months)was better than that in the PD-L1 negative(TC-)group(2.6 months)(p=0.03).9.For stage I-IV CRC patients,there were 43 TC+/TIC+ cases(28.1%),54 TC-/TIC-cases(35.3%),35 TC+/TIC-cases(22.9%),and 21 TC-/TIC+ cases(13.7%).10.The 2 years DFS rates of TC-/TIC+,TC-/TIC-,TC+/TIC+ and TC+/TIC-in stage I-III CRC patients were 80%,77.7%,71.4%and 66.7%,respectively.The median PFS of TC-/TIC+,TC-/TIC-,TC+/TIC-and TC+/TIC+ in stage IV patients were 1 months,3.8 months,6 months,and 7.23 months respectively.11.For stage I-III CRC patients,the TC-/TIC-rate in dMMR patients(35.7%,10/28)was lower than that in pMMR patients(51.9%,40/77)and the TC+/TIC+in dMMR patients(25%,7/28)was higher than that in pMMR patients(7.8%,6/46).For stage I-III CRC patients,the percentages of TC+/TC+ and TC-/TIC-in dMMR/pMMR patients were different(p=0.036).For Stage Ⅰ-Ⅲ patients,TC/TIC may be correlated with dMMR/pMMR(p=0.01).Conclusion:The positive rate of PD-LI expression in tumor cells and tumor infiltrating immune cells increased with the increase of stages classification.Forpatients of stage I-IV,the tumor immune cells infiltrating level may be related to the expression of PD-L1 in tumor infiltrating immune cells.For stage I-III patients,dMMR/pMMR may not be related to PD-L1 expression in tumor cells.The percentage of TC+/TC+ and TC-/TIC-may be different for dMMR/pMMR colorectal cancer patients of stage Ⅰ-Ⅲ.