The Expression And Clinical Pathological Significance Of HHLA2 And PD-L1 In Colorectal Carcinomas Tissues

Purpose:It is an important scientific problem to find new immunotherapy targets to expand the beneficiary population and new biomarkers to more accurately predict the efficacy of PD-1/PD-L1 inhibitors.This study attempts to evaluate the possibility of HHLA2 as a new immune pathway for the treatment of colorectal carcinoma by exploring the clinical pathological significance and correlation between the expression of HHLA2 in human colorectal carcinoma tissues.Then,this article further investigates the clinical significance and different expression of PD-L1 in colorectal cancer tumor cells and tumor interstitial immune cells.The correlation between the expression of PD-L1 and HHLA2 expression,TP53 expression,MSI status and the quantity of TAMs was analyzed to search for more precise screening and prediction indicators of PD-1/PD-L1inhibitors.Methods:In this paper,120 cases of colorectal adenocarcinoma tissue wax blocks which were from the Pathology Department of 940 Hospital from March to July 2017and the clinicopathological data of the patients were collected.The expression of HHLA2,PD-L1,TP53,CD68 and CD163 in colorectal carcinoma was detected by tissue chip technology and immunohistochemical staining.SPSS 25.0 software was used to analyze the relationship between each factor,and the clinicopathological characteristics of patients,the prognosis of patients.The correlation between HHLA2and PD-L1 expression was analyzed.The relationship between the number of CD68~+TAMs,CD163~+TAMs and the expression of PD-L1 and HHLA2 was analyzed.Results:1.The expression of PD-L1(T)was related to the tumor’s primary site(P<0.05).PD-L1(I)was inversely related to distant metastases and vascular infiltration groups(P<0.05).Multivariate analysis suggests distant metastasis and PD-L1(T)could be used as independent prognostic risk factors in patients with CRC(P<0.05).2.The positive rate of HHLA2 in colorectal carcinoma tissues was 94.96%,among which weakly expression account for 26.89%,moderately expression account for 47.06%and strongly expression account for 21.01%.The expression of HHLA2 was negatively correlated with the degree of tumor differentiation(r=-0.212,P=0.021).Multivariate regression analysis showed that distant metastasis and HHLA2 can be used as independent risk factors in patients with colorectal carcinoma(P<0.05).3.The expression of PD-L1(T)in CRC was positively correlated with the expression of HHLA2 and TP53(r=0.211,P=0.021)(r=0.234,P=0.018).4.The number of CD68~+TAMs in CRC was negatively correlated with distant metastasis(P<0.05),and the number of CD163~+TAMS was negatively correlated with the depth of infiltration(P<0.05).The number of CD68~+TAMs and CD163~+TAMs were both positively correlated with the expression of PD-L1(T)(r=0.216,P=0.018)(r=0.228,P=0.012).Conclusion:1.HHLA2 is abnormally highly expressed in colorectal carcinoma and it can be used as an independent risk factor for the prognosis of colorectal carcinoma patients.HHLA2 is expected to become a new target for immunotherapy.2.The expression of HHLA2 is positively correlated with expression of PD-L1 in colorectal carcinoma;the expression of PD-L1 is positively correlated with the expression of TP53 and TAMs.HHLA2 and TP53 are expected to be the screening indicators for the applicable population of PD-1/PD-L1 inhibitors.3.The number of tumor-related macrophages is correlated with the degree of invasive growth in colorectal carcinoma.The number of CD68~+TAM and CD163~+TAM is positively correlated with the expression of PD-L1,and it is expected to be a potential predictor of PD-1/PD-L1 immune checkpoint inhibitor therapy for colorectal carcinoma.