少吃点，能抗癌，上海交大Cell子刊论文，揭示热量限制抗癌的新机制

Core Viewpoint - Caloric restriction (CR) has been shown to improve health and potentially extend lifespan in mammals, with a newly identified mechanism involving tumor-infiltrating neutrophils (TIN) and the IGF-1/HIF-1α/HILPDA signaling axis as a target for cancer treatment [3][5][7]. Group 1: Mechanism of Action - CR alters the proportion and gene expression profile of TIN, indicating their critical role in the anti-tumor effects of CR [4]. - The gene expression changes in TIN due to CR are primarily related to lipid processes, particularly downregulating HILPDA, which reduces lipid accumulation in TIN [4][5]. - The reduction of HILPDA expression limits lipid transfer to tumor cells and immune effector cells, thereby inhibiting tumor growth and enhancing anti-tumor immunity [4][5]. Group 2: Signaling Pathway - CR decreases circulating IGF-1 levels, which in turn reduces HIF-1α mRNA expression in neutrophils, leading to lower HILPDA expression in TIN [4][5]. - Patients with low baseline HIF-1α mRNA levels in neutrophils show better responses to combined immunotherapy [4]. Group 3: Implications for Cancer Treatment - The findings establish a new mechanism centered on neutrophils and lipids that explains the tumor-suppressive effects of CR [7]. - The IGF-1/HIF-1α/HILPDA signaling axis is proposed as a novel target for cancer therapy [7].