意大利欧洲肿瘤研究所Teresa Manzo团队发现亚油酸(LA)可增强CD8+ T细胞(CTL)代谢适应度和抗肿瘤免疫。2023年3月9日出版的《细胞—代谢》发表了这项成果。

他们表明LA是一个主要的积极调节CTL活性，通过改善代谢适应度，防止疲劳，并刺激具有卓越效应功能的记忆样表型。他们报道了LA治疗增强er -线粒体接触(MERC)的形成，从而促进钙(Ca2+)信号、线粒体能量学和CTL效应子功能。直接的结果是，LA诱导的CD8 T细胞的抗肿瘤效力在体外和体内都是优越的。因此，他们建议LA治疗作为肿瘤治疗中的过继T细胞治疗(ACT)增强剂。

研究人员表示，代谢状态是一种有效的ACT的主要障碍。事实上，特定的脂质可以损害CTL线粒体的完整性，导致抗肿瘤反应缺陷。然而，脂质在多大程度上影响CTL功能和命运仍未被探索。

附：英文原文

Title: Linoleic acid potentiates CD8+ T cell metabolic fitness and antitumor immunity

Author: Carina B. Nava Lauson, Silvia Tiberti, Paola A. Corsetto, Federica Conte, Punit Tyagi, Markus Machwirth, Stefan Ebert, Alessia Loffreda, Lukas Scheller, Dalia Sheta, Zeinab Mokhtari, Timo Peters, Ayush T. Raman, Francesco Greco, Angela M. Rizzo, Andreas Beilhack, Giovanni Signore, Nicola Tumino, Paola Vacca, Liam A. McDonnell, Andrea Raimondi, Philip D. Greenberg, Johannes B. Huppa, Simone Cardaci, Ignazio Caruana, Simona Rodighiero, Luigi Nezi, Teresa Manzo

Issue&Volume: 2023-03-09

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.

DOI: 10.1016/j.cmet.2023.02.013

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00049-9