High serum sPD-1 and sPD-L1 levels 1 predict outcome in hepatocellular carcinoma patients treated with radiotherapy.

Abstract

e16672 Background: Accumulating data have shown that soluble (s)PD-1 and sPD-L1 are potential biomarkers for the curative efficacy of chemotherapy in several cancers. However, these markers have not been well established for outcomes in hepatocellular carcinoma (HCC) radiotherapy (RT). Therefore, this study aims to assess sPD-1/sPD-L1 levels before and after RT and their relationship to clinical characteristics and prognoses. Methods: Pre-treatment serum sPD-L1 and sPD-1 levels were measured with an enzyme-linked immunosorbent assay (ELISA) in 281 patients with HCC treated with RT. The association between serum sPD-L1 and sPD-1 levels and prognosis was assessed using survival analysis. Formalin-fixed paraffin-embedded samples were obtained from 40 patients with HCC who underwent surgery. The expression of PD-L1 was evaluated by immunohistochemical analysis. Results: Using multivariate analyses; sPD-L1 and sPD-1 levels were significant independent predictors of disease-free and overall survival. Patients with maximum tumor diameters ≥5 cm and Barcelona clinic liver cancer (BCLC) staging B and C had significantly higher median sPD-1/sPD-L1 serum concentrations compared to patients with smaller tumor sizes and earlier stages. There was a positive correlation (r = 0.377, p < 0.001) between sPD-L1 and sPD-1 levels. High pretreatment sPD-1/sPD-L1 levels were associated with poor prognoses, and increased sPD-1/sPD-L1 levels were associated with disease progression after RT. In post-irradiated tumor tissue, PD-L1 expression was significantly higher than matched, non-irradiated tissue. In addition, higher PD-L1 expression was correlated with decreased cytotoxic T-cell infiltration and poor survival. Therefore, sPD-1/sPD-L1 could be used as noninvasive biomarkers for evaluating HCC malignancy before RT and in predicting the response to RT in HCC patients. Conclusions: High pretreatment serum sPD-L1 and sPD-1 were associated with poor prognoses, and increased serum sPD-L1 levels were associated with the disease progression of HCC patients treated with RT. PD-L1/ PD-1 pathway may be explored as therapeutic targets and potential predictive biomarkers for HCC treated with RT.