乳酸一直以来被认为是糖酵解过程末端的代谢废物，最近发现它在代谢和其他方面具有多面功能角色。肿瘤细胞中常见的一种代谢重编程现象，被称为“华黎效应”，导致高水平的有氧糖酵解产生过量的乳酸。这种乳酸不仅作为维持癌细胞生存的底物，还对免疫细胞起作用。然而，它也抑制了肿瘤相关巨噬细胞（TAMs）的功能，TAMs是一类普遍存在于实体肿瘤中的先天免疫细胞，从而促进恶性肿瘤细胞的免疫逃逸。TAMs具有高度可塑性的特点，通常分为促炎性M1表型和促肿瘤M2表型。通过受乳酸的“教育”过程，TAMs倾向于采取免疫抑制表型，并与肿瘤细胞合作促进血管生成。此外，越来越多的证据表明代谢重编程与表观遗传修饰存在联系，这暗示了组蛋白修饰在肿瘤微环境（TME）中多种细胞事件中的参与。在本综述中，我们深入研究了关于肿瘤中乳酸代谢的最新发现，特别关注乳酸对TAMs功能的影响。我们旨在整理乳酸引起的TAM极化和血管生成的分子机制，并探讨TAMs与肿瘤细胞之间的乳酸介导的相互作用。最后，我们还涉及针对糖酵解和乳酸产生的免疫代谢治疗和药物递送策略的最新进展，为未来治疗方法提供新的视角。版权所有 © 2023 陶, 钟, 曾和宋。

Lactate, traditionally regarded as a metabolic waste product at the terminal of the glycolysis process, has recently been found to have multifaceted functional roles in metabolism and beyond. A metabolic reprogramming phenomenon commonly seen in tumor cells, known as the "Warburg effect," sees high levels of aerobic glycolysis result in an excessive production of lactate. This lactate serves as a substrate that sustains not only the survival of cancer cells but also immune cells. However, it also inhibits the function of tumor-associated macrophages (TAMs), a group of innate immune cells ubiquitously present in solid tumors, thereby facilitating the immune evasion of malignant tumor cells. Characterized by their high plasticity, TAMs are generally divided into the pro-inflammatory M1 phenotype and the pro-tumour M2 phenotype. Through a process of 'education' by lactate, TAMs tend to adopt an immunosuppressive phenotype and collaborate with tumor cells to promote angiogenesis. Additionally, there is growing evidence linking metabolic reprogramming with epigenetic modifications, suggesting the participation of histone modification in diverse cellular events within the tumor microenvironment (TME). In this review, we delve into recent discoveries concerning lactate metabolism in tumors, with a particular focus on the impact of lactate on the function of TAMs. We aim to consolidate the molecular mechanisms underlying lactate-induced TAM polarization and angiogenesis and explore the lactate-mediated crosstalk between TAMs and tumor cells. Finally, we also touch upon the latest progress in immunometabolic therapies and drug delivery strategies targeting glycolysis and lactate production, offering new perspectives for future therapeutic approaches.Copyright © 2023 Tao, Zhong, Zeng and Song.