Major Histocompatibility Complex (MHC) Class I-associated phosphopeptides as potential targets for immunotherapy in hepatocellular carcinoma (HCC)

Despite the high incidence of HCC, being the fifth most common cancer worldwide, current therapeutic options remain limited for advanced HCC. There is, however, first evidence of clinical improvement after checkpoint blockade and it has also been shown that CD8+ T-cell responses targeting tumor antigens beneficially impact the survival of HCC patients. Immunotherapy therefore seems to be a promising approach for HCC treatment. The identification of tumor-specific antigens provides the basis for the development of an efficient targeted immunotherapy. Of note, until today only few tumor-specific antigens for HCC were identified. Promising proteins that harbor tumor antigens are so called phosphoproteins. This is because phosphoproteins are abundantly integrated in most signaling pathways and dysregulation of signaling pathways including aberrant and increased phosphorylation of proteins represents one hallmark of cancer. These emerging phosphoproteins can be degraded and the derived peptide fragments are presented via MHC-class I molecules on the cell surface of altered cells leading to T-cell recognition. We therefore claim that MHC-class I-associated phosphopeptides are attractive new tumor antigens for CD8+ T-cell-based immunotherapy of HCC.