CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:HLA-DR-Expressing γδ T Cells Facilitate the Anti-Leukemia Activity of αβ T Cells.
HLA-DR-Expressing γδ T Cells Facilitate the Anti-Leukemia Activity of αβ T Cells.
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除了具有显著的细胞毒性能力外,γδ T 细胞还作为连接固有免疫和适应性免疫的桥梁发挥关键作用。尽管 γδ T 细胞已被证明能协调与其他免疫细胞的相互作用,但其在急性髓系白血病(AML)背景下对 αβ T 细胞的影响仍未被探索。
在本研究中,我们发现 αβ T 细胞的功能缺陷与新诊断 AML 患者中 HLA-DR + γδ T 细胞的下调显著相关。Vδ2 + T 细胞是人外周血中 γδ T 细胞的主要亚群,在体外扩增后表现出 HLA-DR 水平升高。
值得注意的是,较低剂量的扩增 Vδ2 + T 细胞并未对 AML 细胞产生直接细胞毒性;相反,它们显著增强了原发性 αβ T 细胞对 AML 细胞的细胞毒性能力。
此外,阻断 Vδ2 + T 细胞上的 HLA-DR 明显削弱了这种促进作用。综上所述,我们的研究结果表明,Vδ2 + T 细胞在抗 AML 免疫中除了直接杀伤能力外还具有重要的间接作用,并为过继性 Vδ2 + T 细胞治疗的潜力提供了新的见解。
In addition to exhibiting significant cytotoxic capabilities, γδ T cells play a crucial role as a bridge between innate and adaptive immunity. Although γδ T cells have been demonstrated to orchestrate interactions with other immune cells, their impact on αβ T cells in the setting of acute myeloid leukemia (AML) remains unexplored.
In this study, we found that functional deficiencies of αβ T cells were significantly associated with the downregulation of HLA-DR + γδ T cells in patients newly diagnosed with AML. Vδ2 + T cells, which constitute a predominant subset of γδ T cells in human peripheral blood, exhibited elevated levels of HLA-DR following ex vivo expansion.
Notably, a lower dose of the expanded Vδ2 + T cells did not induce direct cytotoxicity against AML cells; instead, they significantly enhanced the cytotoxic capacity of primary αβ T cells toward AML cells.
Furthermore, blockade of HLA-DR on Vδ2 + T cells markedly diminished this facilitating effect. Taken together, our findings demonstrate an important indirect role for Vδ2 + T cells beyond their direct killing ability in the context of anti-AML immunity and provide novel insights into the therapeutic potential of adoptive Vδ2 + T cell therapy.
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