The First Affiliated Hospital of Ningbo University, Ningbo 315211, Zhejiang, China.
Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang, China.
Autoimmun Rev. 2024 Jun;23(6):103579. doi: 10.1016/j.autrev.2024.103579. Epub 2024 Jul 14.
The surrounding non-cancer cells and tumor cells that make up the tumor microenvironment (TME) have various metabolic rhythms. TME metabolic heterogeneity is influenced by the intricate network of metabolic control within and between cells. DNA, protein, transport, and microbial levels are important regulators of TME metabolic homeostasis. The effectiveness of immunotherapy is also closely correlated with alterations in TME metabolism. The response of a tumor patient to immunotherapy is influenced by a variety of variables, including intracellular metabolic reprogramming, metabolic interaction between cells, ecological changes within and between tumors, and general dietary preferences. Although immunotherapy and targeted therapy have made great strides, their use in the accurate identification and treatment of tumors still has several limitations. The function of TME metabolic heterogeneity in tumor immunotherapy is summarized in this article. It focuses on how metabolic heterogeneity develops and is regulated as a tumor progresses, the precise molecular mechanisms and potential clinical significance of imbalances in intracellular metabolic homeostasis and intercellular metabolic coupling and interaction, as well as the benefits and drawbacks of targeted metabolism used in conjunction with immunotherapy. This offers insightful knowledge and important implications for individualized tumor patient diagnosis and treatment plans in the future.
肿瘤微环境（TME）中的周围非癌细胞和肿瘤细胞具有各种代谢节律。TME 代谢异质性受细胞内和细胞间代谢控制复杂网络的影响。DNA、蛋白质、运输和微生物水平是 TME 代谢平衡的重要调节剂。免疫疗法的有效性也与 TME 代谢的改变密切相关。肿瘤患者对免疫疗法的反应受到多种变量的影响，包括细胞内代谢重编程、细胞间代谢相互作用、肿瘤内和肿瘤间的生态变化以及一般的饮食偏好。尽管免疫疗法和靶向疗法已经取得了很大的进展，但它们在肿瘤的准确识别和治疗中的应用仍存在一些局限性。本文总结了 TME 代谢异质性在肿瘤免疫治疗中的作用。它重点讨论了肿瘤进展过程中代谢异质性的发展和调节，细胞内代谢平衡和细胞间代谢偶联和相互作用失衡的精确分子机制和潜在临床意义，以及与免疫疗法联合使用的靶向代谢的优缺点。这为未来个体化肿瘤患者诊断和治疗计划提供了有见地的知识和重要启示。
