Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects
Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects
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DOI：
10.1016/j.celrep.2022.111256
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发表时间：
2022-08-23
期刊：
影响因子：
8.8
通讯作者：
Longo, Valter D.
中科院分区：
文献类型：
--
作者：
Cortellino, Salvatore;Raveane, Alessandro;Longo, Valter D.
免疫疗法正在改善癌症患者的预后和生存率，但尽管在不同癌症中取得了令人鼓舞的结果，但大多数肿瘤对其具有耐药性，并且免疫疗法组合通常伴有严重的副作用。在这里，我们表明，周期性禁食模仿饮食（FMD）可以作用于肿瘤微环境，并通过扩增早期耗竭的效应T细胞，将癌症代谢从糖酵解转换为呼吸，并减少胶原沉积来增加免疫疗法（抗PD-L1和抗OX 40）对免疫原性差的三阴性乳腺肿瘤（TNBC）的疗效。此外，FMD通过防止免疫应答的过度激活来减少免疫相关不良事件（irAE）的发生。这些结果表明，FMD周期具有增强抗癌免疫应答的功效、扩大对免疫疗法敏感的肿瘤部分并减少其副作用的潜力。
Immunotherapy is improving the prognosis and survival of cancer patients, but despite encouraging out-comes in different cancers, the majority of tumors are resistant to it, and the immunotherapy combinations are often accompanied by severe side effects. Here, we show that a periodic fasting-mimicking diet (FMD) can act on the tumor microenvironment and increase the efficacy of immunotherapy (anti-PD-L1 and anti-OX40) against the poorly immunogenic triple-negative breast tumors (TNBCs) by expanding early exhausted effector T cells, switching the cancer metabolism from glycolytic to respiratory, and reducing collagen depo-sition. Furthermore, FMD reduces the occurrence of immune-related adverse events (irAEs) by preventing the hyperactivation of the immune response. These results indicate that FMD cycles have the potential to enhance the efficacy of anti-cancer immune responses, expand the portion of tumors sensitive to immuno-therapy, and reduce its side effects.