4.7 Article

The function of MSP-activated γδT cells in hepatocellular carcinoma

Journal

INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 124, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.intimp.2023.110893

Keywords

gamma delta T cells; Hepatocellular carcinoma; MSP; Costimulatory molecules

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Immunotherapeutic strategies targeting gamma 6T cells show promise in the treatment of hepatocellular carcinoma (HCC). A novel HCC protein antigen called MSP, which activates gamma 6T cells, was identified in this study. The activated gamma 6T cells were found to kill HCC cells through direct and indirect mechanisms, providing a potential new target for clinical diagnosis and treatment of HCC.
Immunotherapeutic strategies targeting gamma 6T cells are now recognized as a promising treatment method for hepatocellular carcinoma (HCC). To date, no specific antigen or antigenic epitope recognized by gamma 6T cells has been identified, limiting their application in the field of HCC treatment. Previously, we used an established screening strategy to identify a novel HCC protein antigen recognized by gamma 6T cells called MSP. In this study, we explored the function of MSP activated-gamma 6T cells in HCC. Results demonstrated that the proportions of gamma 6T cells in the peripheral blood of HCC patients and the level of IFN-gamma in the serum were higher than in healthy controls. We also determined that gamma 6T cells can bind MSP protein. MSP-activated gamma 6T cells were shown to contain a specific CDR362 sequence that supports the recognition of MSP by gamma 6T cells. We determined that MSP is highly expressed in HCC, MSP-activated gamma 6T cells in the peripheral blood of HCC patients express co-stimulatory molecules, and MSP-activated gamma 6T cells directly killed HCC cells. In conclusion, we demonstrated that the novel protein ligand MSP activated gamma 6T cells, leading to the killing of HCC cells through direct and indirect mechanisms. These findings could provide a potential new target for the clinical diagnosis and treatment of HCC and a foundation for clinical treatment strategies in HCC.

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