解码肿瘤微环境中的代谢对话:从免疫抑制到精确的癌症治疗。

IF 13.5 1区 医学 Q1 HEMATOLOGY
Ruoli Wang, Jincheng Zhuang, Qi Zhang, Wantao Wu, Xinrui Yu, Hao Zhang, Zongyi Xie
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引用次数: 0

摘要

肿瘤微环境(TME)是免疫细胞和癌细胞争夺必需营养素的代谢战场,最终影响抗肿瘤免疫和治疗结果。最近的研究进展揭示了免疫细胞(包括巨噬细胞、T细胞和dc)的代谢重编程如何决定它们在TME内的功能极化、存活和相互作用。缺氧、酸中毒和营养剥夺等因素驱动免疫细胞向免疫抑制表型发展,而肿瘤和基质细胞之间的代谢相互作用进一步加强了治疗耐药性。这篇综述综合了对调节免疫细胞行为的代谢检查点的新见解,重点关注糖酵解、氧化磷酸化(OXPHOS)、脂质氧化和氨基酸依赖性等过程。我们强调代谢酶(如IDO1, ACLY, CPT1A)和代谢物(如乳酸,犬尿氨酸)如何促进免疫逃避,并提出逆转这些途径的策略。单细胞代谢组学、空间分析和人工智能驱动的药物发现等创新正在改变我们对代谢异质性及其临床意义的理解。此外,我们讨论了尖端的治疗方法-从双靶向代谢抑制剂到基于生物材料的递送系统-旨在重编程免疫细胞代谢和提高免疫治疗的有效性。尽管临床前研究前景看好,但将这些发现转化为临床应用仍然存在挑战,包括生物标志物验证、代谢可塑性和患者间可变性。通过将机制发现与转化应用联系起来,本综述强调了免疫代谢靶向治疗克服耐药性和重新定义精确肿瘤学的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Decoding the metabolic dialogue in the tumor microenvironment: from immune suppression to precision cancer therapies.

The tumor microenvironment (TME) represents a metabolic battleground where immune cells and cancer cells vie for essential nutrients, ultimately influencing antitumor immunity and treatment outcomes. Recent advancements have shed light on how the metabolic reprogramming of immune cells, including macrophages, T cells, and DCs, determines their functional polarization, survival, and interactions within the TME. Factors such as hypoxia, acidosis, and nutrient deprivation drive immune cells toward immunosuppressive phenotypes, while metabolic interactions between tumors and stromal cells further entrench therapeutic resistance. This review synthesizes new insights into the metabolic checkpoints that regulate immune cell behavior, focusing on processes like glycolysis, oxidative phosphorylation (OXPHOS), lipid oxidation, and amino acid dependencies. We emphasize how metabolic enzymes (e.g., IDO1, ACLY, CPT1A) and metabolites (e.g., lactate, kynurenine) facilitate immune evasion, and we propose strategies to reverse these pathways. Innovations such as single-cell metabolomics, spatial profiling, and AI-driven drug discovery are transforming our understanding of metabolic heterogeneity and its clinical implications. Furthermore, we discuss cutting-edge therapeutic approaches-from dual-targeting metabolic inhibitors to biomaterial-based delivery systems-that aim to reprogram immune cell metabolism and enhance the effectiveness of immunotherapy. Despite the promise in preclinical studies, challenges persist in translating these findings to clinical applications, including biomarker validation, metabolic plasticity, and interpatient variability. By connecting mechanistic discoveries with translational applications, this review highlights the potential of immunometabolic targeting to overcome resistance and redefine precision oncology.

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来源期刊
CiteScore
12.60
自引率
7.30%
发文量
97
审稿时长
6 weeks
期刊介绍: Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings. Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.
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