Abstract
e15680 Background: Adjuvant cytokine-induced killer cell (CIK) treatment has shown potential in reducing recurrence rate and prolong survival of patients with hepatocellular carcinoma (HCC). We aim to evaluate the PD-1/PD-L1 expression in tumor cells and tumor infiltrative lymphocytes in HCC patients and their correlation with survival benefit from cytokine-induced killer cell therapy. Methods: Between 2004 and 2011, 290 HCC patients received curative section were retrospectively enrolled by one-to-one propensity score matching, including 145 cases received adjuvant CIK cell transfusion after surgery (Surgery-CIK group), and 145 cases underwent surgery only (Surgery only group). Immunohistochemistry (IHC) was used to measure the PD-1 and PD-L1 expression in formalin fixed paraffin embedded tissue of all subjects; IHC of CD4, CD8 and Foxp3 were also conducted in the surgery-CIK group to explore their correlation with PD1/PD-L1 expression and survival of HCC patients. Results: The surgery-CIK group had significantly improved overall survival (OS; HR 0.55, 95% CI 0.33-0.92) and disease-free survival (DFS; HR 0.59, 95% CI 0.42-0.83) as compared to the surgery-only group. In the surgery-CIK group, univariate analysis showed both high PD-L1 expression and a high number of PD-1+ TILs were significantly associated with improved OS, while only the high number of PD-1+ TILs was associated with improved DFS. Multivariate analyses showed a high number of PD-1+ TILs was the only independent factor predicting favorable OS (HR 0.19, 95% CI 0.08-0.45) and DFS (HR 0.40, 95% CI 0.24-0.66) in the surgery-CIK group. By contrast, in the surgery-only group, no significant associations between PD-1/PD-L1 expression and survival of patients were identified. Conclusions: A high number of PD-1+ TILs can serve as a potent biomarker to adopt CIK cell therapy in HCC patients after curative resection.
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