美国斯隆凯特琳学院Joseph C. Sun研究团队发现，禁食重塑组织特异性生态位，以改善NK细胞介导的抗肿瘤免疫活性。2024年6月14日，国际知名学术期刊《免疫》发表了这一成果。

禁食与改善癌症预后有关。研究人员研究了禁食对自然杀伤(NK)细胞抗肿瘤免疫活性的影响。循环禁食以依赖NK细胞的方式改善对实体和转移性肿瘤的免疫活性。在禁食期间，NK细胞从外周组织重新分布到骨髓(BM)。在人类中，禁食也会减少循环NK细胞的数量。禁食小鼠脾脏中的NK细胞通过脂肪酸和糖皮质激素浓度升高进行代谢重组，通过增加CPT1A酶的表达来增加脂肪酸代谢，Cpt1a缺失会损害NK细胞的存活和功能。

同样，NK细胞在禁食期间重新分布到BM需要转运介质S1PR5和CXCR4。这些细胞被表达白细胞介素(IL)-12的骨髓细胞增加，从而提高IFN-γ的产生。他们的发现确定了饮食限制和优化先天免疫反应之间的联系，具有增强免疫治疗策略的潜力。

附：英文原文

Title: Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity

Author: Rebecca B. Delconte, Mark Owyong, Endi K. Santosa, Katja Srpan, Sam Sheppard, Tomi J. McGuire, Aamna Abbasi, Carlos Diaz-Salazar, Jerold Chun, Inez Rogatsky, Katharine C. Hsu, Stefan Jordan, Miriam Merad, Joseph C. Sun

Issue&Volume: 2024-06-14

Abstract: Fasting is associated with improved outcomes in cancer. Here, we investigated theimpact of fasting on natural killer (NK) cell anti-tumor immunity. Cyclic fastingimproved immunity against solid and metastatic tumors in an NK cell-dependent manner.During fasting, NK cells underwent redistribution from peripheral tissues to the bonemarrow (BM). In humans, fasting also reduced circulating NK cell numbers. NK cellsin the spleen of fasted mice were metabolically rewired by elevated concentrationsof fatty acids and glucocorticoids, augmenting fatty acid metabolism via increasedexpression of the enzyme CPT1A, and Cpt1a deletion impaired NK cell survival and function in this setting. In parallel, redistributionof NK cells to the BM during fasting required the trafficking mediators S1PR5 andCXCR4. These cells were primed by an increased pool of interleukin (IL)-12-expressingBM myeloid cells, which improved IFN-γ production. Our findings identify a link between dietary restriction and optimized innate immune responses, with the potential to enhance immunotherapy strategies.

DOI: 10.1016/j.immuni.2024.05.021

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00275-9