Data from Fasting-Mimicking Diet Drives Antitumor Immunity against Colorectal Cancer by Reducing IgA-Producing Cells

• DOI: 10.1158/0008-5472.c.6908354.v1
• Publication Date: 2023-11-01T08:01:19Z
• Authors: Ziwen Zhong; Hao Zhang; Ke Nan; Jing Zhong; Qichao Wu; Lihong Lu; Ying Yue; Zhenyu Zhang; Miaomiao Guo; Zhiqiang Wang; Jie Xia; Yun Xing; Ying Fu; Baichao Yu; Wenchang Zhou; Xingfeng Sun; Yang Shen; Wankun Chen; Jie Zhang; Jin Zhang; Duan Ma; Yiwei Chu; Ronghua Liu; Changhong Miao

<div>Abstract<p>As a safe, feasible, and inexpensive dietary intervention, fasting-mimicking diet (FMD) exhibits excellent antitumor efficacy by regulating metabolism boosting immunity. A better understanding of the specific mechanisms underlying immunoregulatory functions FMD could help improve expand clinical application FMD-mediated immunotherapeutic strategies. In this study, we aimed to elucidate role metabolic reprogramming induced in activation immunity against colorectal cancer. Single-cell RNA sequencing analysis intratumoral immune cells revealed that tumor-infiltrating IgA<sup>+</sup> B were significantly reduced treatment, leading tumor regression murine cancer models. Mechanistically, delayed growth repressing B-cell class switching IgA. Therefore, FMD-induced reduction overcame suppression CD8<sup>+</sup> T cells. The effects intervention reversed transfer. Moreover, boosted fatty acid oxidation (FAO) trigger RUNX3 acetylation, thus inactivating C<sub>α</sub> gene transcription IgA switching. expansion was also impeded patients placed on FMD, while expression carnitine palmitoyl transferase 1A (CPT1A), rate-limiting enzyme FAO, increased. Furthermore, CPT1A negatively correlated with both secretion within Together, these results highlight holds great promise for treating degree cell infiltration FAO-associated status are potential biomarkers evaluating efficacy.</p>Significance:<p>Metabolic suppresses production activate inhibit growth.</p><p><i><a href="https://aacrjournals.org/cancerres/article/doi/10.1158/0008-5472.CAN-23-2257" target="_blank">See related commentary Bush Perry, p. 3493</a></i></p></div>