Synergistic Effect of PD-L1 and HLA Class I On Prognosis of Patients With Hepatocellular Carcinoma

Abstract Background: Up-regulating the expression of PD-L1 and down-regulating the expression of HLA class I are the two main means of tumor-induced immune tolerance. The purpose of this study is to explore whether there is synergistic effect of up-regulation of PD-L1 and down-regulation of HLA-I on prognosis in hepatocellular carcinoma (HCC). Methods: A cohort of 185 consecutive HCC patients was included in this study. According to the expression of PD-L1 and HLA class I, patients were divided into three subgroups: group A was PD-L1 negative + HLA class I high expression, group B was PD-L1 positive + HLA class I high expression or PD-L1 negative + HLA class I low expression, group C was PD-L1 positive + HLA class I low expression. Results: PD-L1 positive was significantly associated with cirrhosis and tumor-infiltrating lymphocytes (P = 0.026; P= 0.000, respectively). Neither of PD-L1 positive and HLA class I low expression was significantly associated with shorter survival patients (P = 0.116; P = 0.171, respectively). The overall survival time of group C was significantly lower than that of group A and group B (31 months vs 58 months vs 49 months, P = 0.004), which was further confirmed by multivariate Cox regression analysis (group A/B vs group C, HR 3.652, 95%CI 1.627-8.200, P= 0.002). Conclusions: The synergistic effect of PD-L1 positive and HLA class I low expression could result into a significant reduction in survival of patients with HCC, providing theoretical support for the combination of immunotherapy in future.