肿瘤细胞的异常代谢是肿瘤治疗的潜在靶点。在这方面，饮食限制（DR）或其与抗癌药物的组合受到关注，因为它可以阻止肿瘤细胞的生长。除了对肿瘤细胞的作用外，DR还通过调节免疫细胞发挥限制肿瘤生长的外在作用。自然杀伤（NK）细胞是参与肿瘤免疫监视的先天免疫细胞。然而，DR是否可以协助NK细胞控制肿瘤生长仍不确定。在此，我们证明 DR 有效抑制黑色素瘤细胞向肺部的转移。与此相一致的是，在缺乏 NK 细胞的小鼠中，DR 诱导的肿瘤消退最小。单细胞 RNA 测序分析表明，DR 富集了 CD27 CD11b NK 细胞的再生亚群。从机制上讲，DR 激活了涉及转录因子 Eomesodermin (Eomes) 的调节网络，这对于 NK 细胞的发育至关重要。首先，DR通过优化mTORC1信号传导促进Eomes的表达。 Eomes 的上调通过抵消 T-bet 和下游 Zeb2 的表达来恢复功能性 CD27 CD11b NK 细胞亚群。此外，DR 通过增加 Eomes 对染色质的可及性来增强 NK 细胞的功能和趋化性，从而导致粘附分子和趋化因子的表达升高。因此，我们得出结论，DR 疗法通过非肿瘤自主机制增强肿瘤免疫，包括促进 NK 细胞肿瘤免疫监视和激活。

Abnormal metabolism in tumor cells represents a potential target for tumor therapy. In this regard, dietary restriction (DR) or its combination with anticancer drugs is of interest as it can impede the growth of tumor cells. In addition to its effects on tumor cell, DR also plays an extrinsic role in restricting tumor growth by regulating immune cells. Natural killer (NK) cells are innate immune cells involved in tumor immunosurveillance. However, it remains uncertain whether DR can assist NK cells in controlling tumor growth. Herein, we demonstrate that DR effectively inhibits metastasis of melanoma cells to the lung. Consistent with this, the regression of tumors induced by DR was minimal in mice lacking NK cells. Single-cell RNA sequencing analysis revealed that DR enriched a rejuvenated subset of CD27+CD11b+ NK cells. Mechanistically, DR activated a regulatory network involving the transcription factor Eomesodermin (Eomes), which is essential for NK-cell development. Firstly, DR promoted the expression of Eomes by optimizing mTORC1 signaling. The upregulation of Eomes revived the subset of functional CD27+CD11b+ NK cells by counteracting the expression of T-bet and downstream Zeb2. Moreover, DR enhanced the function and chemotaxis of NK cells by increasing the accessibility of Eomes to chromatin, leading to elevated expression of adhesion molecules and chemokines. Consequently, we conclude that DR therapy enhances tumor immunity through non-tumor autonomous mechanisms, including promoting NK-cell tumor immunosurveillance and activation.