IM-3对γδT细胞抗急性髓系白血病功能的研究

Objective: This study aims to systematically compare the functional changes in anti-AML tumor activity between γδ T cells and αβ T cells under TIM-3 knockdown conditions, with a focus on elucidating the role of TIM-3 in regulating γδ T cell-mediated anti-AML effects and identifying underlying mechanisms. The findings aim to provide foundational data for developing novel γδ T cell-based immunotherapies with clinical translation potential for targeted AML treatment.Methods: TIM-3 knockdown was achieved using CRISPR/Cas9 technology. Flow cytometry was employed to evaluate sustained anti-tumor activity against AML cells, expression levels of early and late activation markers, and changes in cytokine secretion profiles in co-culture supernatants of γδ T cells and αβ T cells before and after TIM-3 knockdown.Results: TIM-3 knockdown γδ T cells were successfully generated. TIM-3 deficiency significantly impaired the in vitro AML-killing capacity of γδ T cells, accompanied by reduced cytokine secretion and diminished activation levels.Conclusion: TIM-3 knockdown markedly suppresses the anti-AML efficacy of γδ T cells, characterized by decreased release of functional cytokines and reduced activation. These results demonstrate that TIM-3 expression in γδ T cells is essential for maintaining their anti-tumor functionality, highlighting its potential as a therapeutic target for enhancing γδ T cell-based immunotherapies against AML.