5). In the analysis of the total of each type of TAA-derived peptide-specific T cells, the frequency decreased in 14/16 (87.5%) patients analyzed, and most of them showed fewer than 50 specific spots per 3 × 105 PBMCs, with the exception of one patient. In contrast, the frequencies of CMV-derived peptide-specific T cells were maintained in most of the patients. In recent years, HCC-specific TAAs and their T cell epitopes have been identified, which has made analysis of immunological status in HCC patients

possible and shown that TAA-specific T cell responses can be detected in peripheral blood.11, 18-20 The immunological analysis of HCC patients with RFA using 11 TAA-derived peptides in this study showed that the enhancement of TAA-specific T cell responses occurred in this website 62.3% of patients, the antigens and their epitope to which enhanced T cell responses occurred were diverse, and some of them were newly induced. The mechanism of enhancement click here of tumor-specific immune response by RFA is still unclear. den Brok et al.5 showed that RFA created an antigen source for antitumor immunity by destruction of tumor cells using a mouse tumor model. The antigens used in this study have been reported to be located in the cell

membrane (MRP3), cytoplasm (SART2 and AFP), and nucleus (hTERT and SART3).21-24 The diversity of the target proteins of enhanced T cells suggests that the central mechanism of enhancement of tumor-specific immune response by RFA is due to tumor cell destruction, which supports the results mentioned previously.5 In the present study, we also showed that the number of TAA-specific T cells after RFA was associated with the HCC recurrence-free survival of patients. The univariate and multivariate analyses clearly showed it was a predictive factor for HCC recurrence after RFA. These results suggest that TAA-specific T cells induced by RFA contribute to protection from HCC recurrence, and additional

immunological approaches should be applied to enhance the protective effect after treatment. To understand the precise mechanism that RFA enhances TAA-specific T cell responses, we analyzed the factors that affected Histone demethylase the number of TAA-specific T cells after RFA. Among the factors analyzed, the frequency of CD14+HLA-DR−/low MDSCs after RFA was inversely correlated with the number of TAA-specific T cells, suggesting these MDSCs may have a negative effect on TAA-specific immune responses. Regarding the function of MDSCs in cancer patients, it has been reported that they inhibit T lymphocyte responses.25 In HCC patients, it is reported that the frequency of CD14+HLA-DR−/low MDSCs in PBMCs is significantly increased in comparison with healthy controls and they exert immunosuppressive function via induction of regulatory T cells.26 Taken together with our results, these reports suggest that an additional immunological approach to inhibit the function of MDSCs after RFA may enhance TAA-specific immune responses.