Identification of new potential antigen recognized by γδT cells in hepatocellular carcinoma

In recent years, the application of chimeric antigen receptor T-cell (CAR-T) therapy based on gamma delta T (gamma delta T) cells in hepatocellular carcinoma (HCC) immunotherapy has attracted more and more attention. However, specific antigens recognized by gamma delta T cells are rarely identified, which has become the main restriction on such therapeutic application of gamma delta T cells. In this report, we identified a new peptide and protein antigen recognized by gamma delta T cells in HCC using our previous established strategy. First, we investigated the diversity of the gamma 9/delta 2 T-cell immunorepertoire by sequence analyses of the expressed complementarity-determining region 3 (CDR3) in HCC patients. Then, we constructed gamma 9/delta 2 T-cell receptor (TCR)-transfected cell lines expressing significant HCC CDR3 sequence and identified a series of peptides capable of binding to gamma delta T cells specifically. Next, we identified, further tested and verified the biological functions of these peptides and their matched protein by bioinformatics analysis. We identified that the new protein hepatocyte growth factor-like protein, also called as macrophage-stimulating protein (MSP), and peptide HP1, not only bound to HCC-predominant gamma delta TCR but also effectively activated gamma delta T cells isolated from HCC patients. Moreover, they could stimulate gamma delta T cells in peripheral blood from HCC patients to produce cytokines, which contributed to inhibiting HCC and played an important role in mediating cytotoxicity to HCC cell lines. In conclusion, we identified MSP and HP1, which showed potential as candidates for antigens recognized by gamma delta T cells in HCC.

Automated summary

The research team identified a new peptide and protein antigen recognized by gamma delta T cells in hepatocellular carcinoma, providing a new potential therapeutic target for immunotherapy.