Combination of Intratumoral Invariant Natural Killer T Cells and Interferon-Gamma Is Associated with Prognosis of Hepatocellular Carcinoma after Curative Resection

Purpose: To investigate the prognostic value of intratumoral invariant natural killer T (iNKT) cells and interferon-gamma (IFN-gamma) in hepatocellular carcinoma (HCC) after curative resection. Experimental Design: Expression of TRAV10, encoding the V alpha 24 domain of iNKT cells, and IFN-gamma mRNA were assessed by quantitative real-time polymerase chain reaction in tumor from 224 HCC patients undergoing curative resection. The prognostic value of these two and other clinicopathologic factors was evaluated. Results: Either intratumoral iNKT cells and IFN-gamma alone or their combination was an independent prognostic factor for OS (P = 0.001) and RFS (P = 0.001) by multivariate Cox proportional hazards analysis. Patients with concurrent low levels of iNKT cells and IFN-gamma had a hazard ratio (HR) of 2.784 for OS and 2.673 for RFS. The areas under the curve of iNKT cells, IFN-gamma and their combination were 0.618 vs 0.608 vs 0.654 for death and 0.591 vs 0.604 vs 0.633 for recurrence respectively by receiver operating characteristic curve analysis. The prognosis was the worst for HCC patients with concurrent low levels of iNKT cells and IFN-gamma, which might be related with more advanced pTNM stage and more vascular invasion. Conclusions: Combination of intratumoral iNKT cells and IFN-gamma is a promising independent predictor for recurrence and survival in HCC, which has a better power to predict HCC patients' outcome compared with intratumoral iNKT cells or IFN-gamma alone.