作为一种安全、可行且廉价的膳食干预措施，模仿禁食饮食（FMD）通过调节代谢和增强抗肿瘤免疫力表现出卓越的抗肿瘤功效。深入了解FMD免疫调节功能的具体机制有助于改善和扩展FMD介导的免疫治疗策略的临床应用。本研究旨在阐明FMD诱导的代谢重编程在激活抗结肠癌（CRC）的抗肿瘤免疫中的作用。通过单细胞RNA测序（scRNA-seq）分析肿瘤内免疫细胞，发现FMD治疗显著减少了肿瘤浸润的IgA+ B细胞，从而激活抗肿瘤免疫并在小鼠CRC模型中实现肿瘤消退。机制上，FMD通过抑制B细胞的IgA型类切换延迟肿瘤生长。因此，FMD导致的IgA+ B细胞减少克服了CD8+ T细胞的抑制。通过IgA+ B细胞转移，FMD介导的免疫调节和抗肿瘤效应得以逆转。此外，FMD通过提升脂肪酸氧化（FAO）触发RUNX3乙酰化，从而失活Cα基因转录和IgA型类切换。在接受FMD治疗的患者中，IgA+ B细胞扩增也受到阻碍，而B细胞对FAO的速率限制性酶CPT1A的表达增加。此外，CPT1A表达与CRC中的IgA+ B细胞和IgA分泌呈负相关。综上，这些结果突显出FMD在治疗CRC方面的巨大潜力。此外，IgA+ B细胞浸润程度和与FAO相关的代谢状态可作为评估FMD疗效的潜在生物标志物。

As a safe, feasible, and inexpensive dietary intervention, fasting-mimicking diet (FMD) exhibits excellent antitumor efficacy by regulating metabolism and boosting antitumor immunity. A better understanding of the specific mechanisms underlying the immunoregulatory functions of FMD could help improve and expand the clinical application of FMD-mediated immunotherapeutic strategies. In this study, we aimed to elucidate the role of metabolic reprogramming induced by FMD in activation of antitumor immunity against colorectal cancer (CRC). Single-cell RNA sequencing (scRNA-seq) analysis of intratumoral immune cells revealed that tumor-infiltrating IgA+ B cells were significantly reduced by FMD treatment, leading to the activation of antitumor immunity and tumor regression in murine CRC models. Mechanistically, FMD delayed tumor growth by repressing B cell class switching to IgA. Therefore, FMD-induced reduction of IgA+ B cells overcame the suppression of CD8+ T cells. The immunoregulatory and antitumor effects of FMD intervention were reversed by IgA+ B cell transfer. Moreover, FMD boosted fatty acid oxidation (FAO) to trigger RUNX3 acetylation, thus inactivating Cα gene transcription and IgA class switching. IgA+ B cell expansion was also impeded in patients placed on FMD, while B cell expression of CPT1A, the rate-limiting enzyme of FAO, was increased. Furthermore, CPT1A expression was negatively correlated with both IgA+ B cells and IgA secretion within CRC. Together, these results highlight that FMD holds great promise for treating CRC. Furthermore, the degree of IgA+ B cell infiltration and FAO-associated metabolic status are potential biomarkers for evaluating FMD efficacy.