免疫治疗策略针对γδT细胞的靶向已被认为是肝细胞癌（HCC）的一种有希望的治疗方法。迄今为止，尚未确定γδT细胞识别的特定抗原或抗原表位，限制了它们在HCC治疗领域的应用。我们先前采用一个已建立的筛选策略确定了一种被γδT细胞识别的新型HCC蛋白抗原MSP。本研究探讨了MSP激活的γδT细胞在HCC中的功能。结果表明，HCC患者外周血γδT细胞的比例和血清中的IFN-γ水平均高于健康对照组。我们还确定了γδT细胞能与MSP蛋白结合。MSP激活的γδT细胞显示具有特定的CDR3δ2序列，支持γδT细胞对MSP的识别。我们确定MSP在HCC中高度表达，HCC患者外周血中的MSP激活γδT细胞表达共刺激分子，并且MSP激活的γδT细胞能直接杀伤HCC细胞。综上所述，我们证明了新蛋白配体MSP激活了γδT细胞，并通过直接和间接机制导致了对HCC细胞的杀伤。这些发现可为HCC的临床诊断和治疗提供潜在的新靶点，并为HCC的临床治疗策略奠定基础。Copyright © 2023 Elsevier B.V. All rights reserved.

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.Copyright © 2023 Elsevier B.V. All rights reserved.