Novel Molecular Targets for Hepatocellular Carcinoma

SIMPLE SUMMARY: HCC is a disease with highly unmet medical needs. Specific target antigens for the development of active (vaccine) and/or passive (adoptive T-cell therapy) cancer immunotherapy strategies are needed. The aim of our study was to exploit the high number of data derived from a public dataset to identify HCC-specific overexpressed proteins, leading to potential epitopes recognized by CD8(+) cytotoxic T cells, which may share homology to viral epitopes. Circulating CD8(+) T cells were revealed to be targeting both HCC and viral-related epitopes, suggesting the possible use in HCC-specific immunotherapies. ABSTRACT: Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer globally. Indeed, only a few treatments are available, most of which are effective only for the early stages of the disease. Therefore, there is an urgent needing for potential markers for a specifically targeted therapy. Candidate proteins were selected from datasets of The Human Protein Atlas, in order to identify specific tumor-associated proteins overexpressed in HCC samples associated with poor prognosis. Potential epitopes were predicted from such proteins, and homology with peptides derived from viral proteins was assessed. A multiparametric validation was performed, including recognition by PBMCs from HCC-patients and healthy donors, showing a T-cell cross-reactivity with paired epitopes. These results provide novel HCC-specific tumor-associated antigens (TAAs) for immunotherapeutic anti-HCC strategies potentially able to expand pre-existing virus-specific CD8(+) T cells with superior anticancer efficacy.