Abstract：
The metabolic state represents a major hurdle for an effective adoptive T cell therapy (ACT). Indeed, specific lipids can harm CD8+ T cell (CTL) mitochondrial integrity, leading to defective antitumor responses. However, the extent to which lipids can affect the CTL functions and fate remains unexplored. Here, we show that linoleic acid (LA) is a major positive regulator of CTL activity by improving metabolic fitness, preventing exhaustion, and stimulating a memory-like phenotype with superior effector functions. We report that LA treatment enhances the formation of ER-mitochondria contacts (MERC), which in turn promotes calcium (Ca2+) signaling, mitochondrial energetics, and CTL effector functions. As a direct consequence, the antitumor potency of LA-instructed CD8 T cells is superior in vitro and in vivo. We thus propose LA treatment as an ACT potentiator in tumor therapy.
摘要：
代谢状态代表了有效的过继性T细胞疗法(ACT)的主要障碍。的确,特异性脂质可损害CD8+T细胞（CTL）线粒体完整性，导致有缺陷的抗肿瘤反应。然而,脂质可影响CTL功能和命运的程度仍未研究。这里,我们表明，亚油酸（LA）是CTL活性的主要正调节剂，通过改善代谢适应性，防止精疲力竭，并刺激具有优越效应子功能的记忆样表型。我们报道LA治疗增强ER-线粒体接触（MERC）的形成，反过来促进钙（Ca2+）信号，线粒体能量学，和CTL效应子功能。作为一个直接的后果,LA指导的CD8T细胞在体外和体内的抗肿瘤效力均较高。因此，我们建议将LA治疗作为肿瘤治疗中的ACT增效剂。
