美国丹娜-法伯癌症研究所Anthony Letai、Rongqing Pan团队发现，可以通过靶向线粒体凋亡途径增强基于自然杀伤(NK)细胞的免疫疗法。2022年4月20日出版的《细胞》发表了这项成果。

研究人员发现线粒体凋亡(mtApoptosis)途径对于有效的NK杀伤至关重要，尤其是在与生理相关效应物与靶标比率情况下杀伤效果显著。此外，NK细胞可以引发癌细胞mtApoptosis，线粒体引发状态影响了癌细胞对NK诱导杀伤的易感性。有趣的是，预激活NK细胞赋予它们对BH3模似物的抵抗力。将BH3模拟物与NK细胞结合可在体外协同杀死癌细胞并在体内抑制肿瘤生长。该方法使用的理想BH3模拟物可以通过BH3分析来预测。

该研究揭示了一种合理且精确用来增强NK免疫疗法的策略，该策略也可能适用于T细胞免疫疗法的优化。

据了解，利用NK细胞进行癌症免疫治疗具有广阔的前景。然而，在大多数试验中，基于NK细胞的免疫疗法效果十分有限。因此，急需新的策略来增强NK细胞的杀伤效力。

附：英文原文

Title: Augmenting NK cell-based immunotherapy by targeting mitochondrial apoptosis

Author: Rongqing Pan, Jeremy Ryan, Deng Pan, Kai W. Wucherpfennig, Anthony Letai

Issue&Volume: 2022-04-20

Abstract: Interest in harnessing natural killer (NK) cells for cancer immunotherapy is rapidlygrowing. However, efficacy of NK cell-based immunotherapy remains limited in mosttrials. Strategies to augment the killing efficacy of NK cells are thus much needed.In the current study, we found that mitochondrial apoptosis (mtApoptosis) pathwayis essential for efficient NK killing, especially at physiologically relevant effector-to-targetratios. Furthermore, NK cells can prime cancer cells for mtApoptosis and mitochondrialpriming status affects cancer-cell susceptibility to NK-mediated killing. Interestingly,pre-activating NK cells confers on them resistance to BH3 mimetics. Combining BH3mimetics with NK cells synergistically kills cancer cells in vitro and suppresses tumor growth in vivo. The ideal BH3 mimetic to use in such an approach can be predicted by BH3 profiling.We herein report a rational and precision strategy to augment NK-based immunotherapy,which may be adaptable to T cell-based immunotherapies as well.

DOI: 10.1016/j.cell.2022.03.030

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00340-3