Vγ9Vδ2 T 细胞是有效但难以捉摸的细胞毒性效应器。嗜乳酪蛋白亚家族 2 成员 A1 (BTN2A1) 是一种表面蛋白，最近被证明可以结合 γδ T 细胞受体 (TCR) 的 Vγ9 链，但其在调节 Vγ9Vδ2 T 细胞功能中的确切作用仍不清楚。在这里，我们表明，单克隆 BTN2A1 激动剂抗体 107G3B5 能够显着增强 Vγ9Vδ2 T 细胞针对血液或实体细胞系以及针对成人急性淋巴细胞白血病患者的原代细胞的功能。应用于全息显微镜视频的新计算机视觉策略表明，107G3B5 以定量和定性的方式增强了 Vγ9Vδ2 T 细胞与靶细胞之间的相互作用。此外，我们发现被107G3B5激活的Vγ9Vδ2 T细胞诱导肿瘤细胞中的caspase 3/7激活，从而引发肿瘤细胞焦亡死亡。总之，这些数据表明，用 107G3B5 靶向 BTN2A1 可通过触发焦亡诱导的免疫原性细胞死亡来增强 Vγ9Vδ2 T 细胞抗肿瘤反应。这些新的基于细胞焦亡的疗法具有刺激免疫系统对抗癌症，特别是“冷”肿瘤的巨大潜力。

Vγ9Vδ2 T cells are potent but elusive cytotoxic effectors. Butyrophilin subfamily 2 member A1 (BTN2A1) is a surface protein that has recently been shown to bind the Vγ9 chain of the γδ T-cell receptor (TCR) but its precise role in modulating Vγ9Vδ2 T-cell functions remains unknown. Here, we show that 107G3B5, a monoclonal BTN2A1 agonist antibody, was able to significantly enhance Vγ9Vδ2 T-cell functions against hematological or solid cell lines and against primary cells from adult acute lymphoblastic leukemia patients. New computer vision strategies applied to holotomographic microscopy videos showed that 107G3B5 enhanced the interaction between Vγ9Vδ2 T cells and target cells in a quantitative and qualitative manner. In addition, we found that Vγ9Vδ2 T cells activated by 107G3B5 induced caspase 3/7 activation in tumor cells, thereby triggering tumor cell death by pyroptosis. Together, these data demonstrate that targeting BTN2A1 with 107G3B5 enhances the Vγ9Vδ2 T-cell antitumor response by triggering the pyroptosis-induced immunogenic cell death. These new pyroptosis-based therapies have great potential to stimulate the immune system to fight cancer, especially "cold" tumors.