Abstract
Simple SummaryHCC 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.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.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common cancer and accounts for8.2% of all cancer-related deaths globally, second only to lung cancer, with more than800,000 new cases and deaths per year [1].Surgery is the most effective treatment for earlystageHCC patients from an intention-to-treat perspective, leading to a 60–80% five-year survival.In more advanced disease stages, loco-regional therapies are recommended, with dramatically lower and highly variable survival rates [2]
In order to identify proteins overexpressed in HCC and not detected in normal liver cells, the Normal Tissue dataset, available at the Human Protein Atlas (https://www.proteinatlas.org/about/download), was searched
The analysis identified 40 proteins with different expression levels in HCC that were absent in all normal tissues (HCC-specific proteins = HSP)
Summary
Hepatocellular carcinoma (HCC) is the fifth most common cancer and accounts for8.2% of all cancer-related deaths globally, second only to lung cancer, with more than800,000 new cases and deaths per year [1].Surgery (e.g., resection and transplantation) is the most effective treatment for earlystageHCC patients from an intention-to-treat perspective, leading to a 60–80% five-year survival.In more advanced disease stages, loco-regional therapies are recommended, with dramatically lower and highly variable survival rates [2]. Hepatocellular carcinoma (HCC) is the fifth most common cancer and accounts for. 8.2% of all cancer-related deaths globally, second only to lung cancer, with more than. 800,000 new cases and deaths per year [1]. Surgery (e.g., resection and transplantation) is the most effective treatment for earlystage. HCC patients from an intention-to-treat perspective, leading to a 60–80% five-year survival. In more advanced disease stages, loco-regional therapies are recommended, with dramatically lower and highly variable survival rates [2]. The tyrosine–kinase inhibitor sorafenib has been the only approved first-line systemic therapy for advanced unresectable HCC. Recently has the inhibitor of vascular endothelial growth factor receptors 1–3, lenvatinib, been approved. Few other drugs have been approved as
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