Specific CD8⁺ T cell responses to HLA-A2 restricted MAGE-A3 p271–279 peptide in hepatocellular carcinoma patients without vaccination

The MAGE-A3 protein, one of the promising tumor antigens for immunotherapy, is highly expressed in human hepatocellular carcinoma (HCC). In this study, we estimated the specific CD8⁺ T cell immune response to MAGE-A3 p271–279 peptide (M3₂₇₁) in the peripheral blood of HCC patients without antigen vaccination in order to evaluate its immunotherapeutic potential in these patients. After expansion in vitro, the functional IFN-γ producing M3₂₇₁ specific CD8⁺ T cells were detected in 30.8% (8/26) of HLA-A2⁺MAGE-A3⁺ HCC patients. The effector CD8⁺ T cells could release cytotoxic molecules of granzyme B and perforin after restimulation with natural HLA-A2⁺MAGE-A3⁺ HCC cell lines in the samples tested. The functional supertype of HLA-A2 in the presentation of HLA-A*0201 restricted M3₂₇₁ peptide has been identified in the Chinese HCC patients of Han ethnicity, that widely expanded the applicability of this tumor peptide vaccine in Chinese HCC patients. Thus, the functionally detectable pre-existence of M3₂₇₁-specific CD8⁺ T cells in HCC patients makes M3₂₇₁ a potential target for immunotherapy in these patients. The responsive CD8⁺ T cells to both NY-ESO-1 and MAGE-A3 antigens provide a rationale for the application of a bivalent vaccine in HCC patients with tumors expressing both antigens.