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The function of MSP-activated γδT cells in hepatocellular carcinoma
Boyu Du1, Ruihong Yu2, Xiaoqing Geng2
1Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan City, Hubei Province, PR China; Biomedical Research Institute, Hubei University of Medicine, Shiyan City, Hubei Province, PR China; Renmin Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, PR China; Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan City, Hubei Province, PR China.
Abstract:
Immunotherapeutic strategies targeting γδT cells are now recognized as a promising treatment method for hepatocellular carcinoma (HCC). To date, no specific antigen or antigenic epitope recognized by γδT 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 γδT cells called MSP. In this study, we explored the function of MSP activated-γδT cells in HCC. Results demonstrated that the proportions of γδT cells in the peripheral blood of HCC patients and the level of IFN-γ in the serum were higher than in healthy controls. We also determined that γδT cells can bind MSP protein. MSP-activated γδT cells were shown to contain a specific CDR3δ2 sequence that supports the recognition of MSP by γδT cells. We determined that MSP is highly expressed in HCC, MSP-activated γδT cells in the peripheral blood of HCC patients express co-stimulatory molecules, and MSP-activated γδT cells directly killed HCC cells. In conclusion, we demonstrated that the novel protein ligand MSP activated γδT 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.
Insights
Researchers identified a novel protein, MSP, that activates gamma delta T cells (γδT cells) to target hepatocellular carcinoma (HCC). This discovery offers a new avenue for HCC immunotherapies and diagnostics.
Area of Science:
- Immunology
- Oncology
- Hepatocellular Carcinoma Research
Background:
- Gamma delta T cells (γδT cells) show promise for hepatocellular carcinoma (HCC) immunotherapy.
- Identifying specific antigens recognized by γδT cells is crucial for advancing HCC treatment.
- Previous work identified a novel HCC antigen, named MSP, recognized by γδT cells.
Purpose of the Study:
- To investigate the function of MSP-activated γδT cells in HCC.
- To explore MSP as a potential target for HCC immunotherapeutic strategies.
Main Methods:
- Screening strategy to identify HCC protein antigen recognized by γδT cells (MSP).
- Analysis of γδT cell proportions and IFN-γ levels in HCC patients.
- Assessment of γδT cell binding to MSP protein.
- Identification of specific CDR3δ2 sequences in MSP-activated γδT cells.
- Evaluation of MSP expression in HCC and co-stimulatory molecule expression on MSP-activated γδT cells.
- In vitro killing assay of HCC cells by MSP-activated γδT cells.
Main Results:
- Elevated proportions of γδT cells and IFN-γ levels in HCC patients compared to healthy controls.
- γδT cells demonstrated binding to MSP protein.
- A specific CDR3δ2 sequence was identified in MSP-activated γδT cells, crucial for MSP recognition.
- High expression of MSP was observed in HCC tissues.
- MSP-activated γδT cells from HCC patients expressed co-stimulatory molecules.
- MSP-activated γδT cells directly induced apoptosis in HCC cells.
Conclusions:
- The novel protein ligand MSP activates γδT cells, mediating HCC cell killing via direct and indirect mechanisms.
- MSP represents a potential new target for HCC clinical diagnosis and treatment.
- These findings lay the groundwork for developing novel clinical treatment strategies for HCC.
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