Fasting-Mimicking Diet Drives Antitumor Immunity against Colorectal Cancer by Reducing IgA-Producing Cells.
Fasting-Mimicking Diet Drives Antitumor Immunity against Colorectal Cancer by Reducing IgA-Producing Cells.
复制标题
假装饮食可通过减少产生IGA的细胞来驱动抗肿瘤免疫力。
DOI：
10.1158/0008-5472.can-23-0323
复制
发表时间：
2023-11-01
期刊：
影响因子：
11.2
通讯作者：
中科院分区：
文献类型：
--
作者：
模拟禁食饮食诱导的B细胞代谢重编程抑制了IgA类的转换和产生，从而激活了抗肿瘤免疫，抑制了肿瘤生长。模拟禁食饮食(FMD)作为一种安全、可行、廉价的饮食干预措施，通过调节代谢和增强抗肿瘤免疫，显示出良好的抗肿瘤效果。更好地了解口蹄疫免疫调节功能的具体机制有助于改进和扩大口蹄疫介导的免疫治疗策略的临床应用。在本研究中，我们旨在阐明FMD诱导的代谢重编程在激活抗结直肠癌抗肿瘤免疫中的作用。瘤内免疫细胞的单细胞RNA测序分析表明，口蹄疫治疗显著减少了肿瘤浸润性IgA+B细胞，从而激活了小鼠结直肠癌模型的抗肿瘤免疫和肿瘤消退。从机理上讲，口蹄疫通过抑制B细胞向免疫球蛋白A的转化而延缓了肿瘤的生长。因此，口蹄疫诱导的IgA+B细胞减少克服了CD8+T细胞的抑制。免疫球蛋白A+B细胞转移逆转了口蹄疫干预的免疫调节和抗肿瘤作用。此外，口蹄疫促进脂肪酸氧化(FAO)触发RUNX3乙酰化，从而抑制Cα基因转录和Ig A类转换。口蹄疫患者的IGA+B细胞增殖也受到抑制，而粮农组织限速酶肉碱棕榈酰转移酶1A(CPT1A)的B细胞表达增加。此外，结直肠癌组织中CPT1a的表达与IgA+B细胞和IgA分泌均呈负相关。总之，这些结果突显了FMD在治疗结直肠癌方面的巨大前景。此外，IgA+B细胞的浸润程度和FAO相关的代谢状态是评估口蹄疫疗效的潜在生物标志物。模拟禁食饮食诱导的B细胞代谢重编程抑制了IgA类的转换和产生，从而激活了抗肿瘤免疫，抑制了肿瘤生长。见布什和佩里的相关评论，第3493页
Metabolic reprogramming of B cells induced by fasting-mimicking diet suppresses IgA class switching and production to activate antitumor immunity and inhibit tumor growth. 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. Single-cell RNA sequencing 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 colorectal cancer 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 carnitine palmitoyl transferase 1A (CPT1A), the rate-limiting enzyme of FAO, was increased. Furthermore, CPT1A expression was negatively correlated with both IgA+ B cells and IgA secretion within colorectal cancer. Together, these results highlight that FMD holds great promise for treating colorectal cancer. Furthermore, the degree of IgA+ B cell infiltration and FAO-associated metabolic status are potential biomarkers for evaluating FMD efficacy. Metabolic reprogramming of B cells induced by fasting-mimicking diet suppresses IgA class switching and production to activate antitumor immunity and inhibit tumor growth. See related commentary by Bush and Perry, p. 3493
影响因子：
3.9
作者：
Fu C;Lu Y;Zhang Y;Yu M;Ma S;Lyu S
通讯作者：
Lyu S