肿瘤微环境中的代谢异质性——免疫治疗的一个新标志
Metabolic heterogeneity in tumor microenvironment - A novel landmark for immunotherapy
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影响因子:8.3
分区:医学1区 Top / 免疫学2区
发表日期:2024 Jun
作者:
Chen Chen, Peng Han, Yanping Qing
DOI:
10.1016/j.autrev.2024.103579
摘要
构成肿瘤微环境（TME）的非癌细胞和肿瘤细胞具有多样的代谢节律。TME代谢异质性受到细胞内外复杂代谢调控网络的影响。DNA、蛋白质、转运和微生物水平是调节TME代谢稳态的重要因素。免疫治疗的效果也与TME代谢的变化密切相关。肿瘤患者对免疫治疗的反应受到多种变量的影响，包括细胞内的代谢重编程、细胞间的代谢相互作用、肿瘤内外的生态变化，以及总体饮食偏好。尽管免疫治疗和靶向治疗已取得巨大进展，但在准确识别和治疗肿瘤方面仍存在一些局限性。本文总结了TME代谢异质性在肿瘤免疫治疗中的作用，重点介绍了代谢异质性如何随着肿瘤的进展而发展和调控，细胞内代谢稳态失衡及细胞间代谢耦合与相互作用的具体分子机制及潜在临床意义，以及靶向代谢结合免疫治疗的优缺点。这为未来个体化肿瘤患者的诊断和治疗方案提供了有价值的见解和重要启示。
Abstract
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.