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文献精选 > 近年高分"肿瘤微环境"研究（IF≥30，近5年）

Immunometabolic Interplay in the Tumor Microenvironment. ​

文献信息 ​

DOI10.1016/j.ccell.2020.09.004
PMID33125860
期刊Cancer cell
影响因子44.5
JCR 分区Q1
发表年份2021
被引次数180
关键词免疫学, 免疫代谢学, 体外模型, 代谢, 代谢组学
文献类型Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
ISSN1535-6108
页码28-37
期号39(1)
作者Irem Kaymak, Kelsey S Williams, Jason R Cantor, Russell G Jones

一句话小结 ​

研究表明，肿瘤微环境中的复杂因素显著影响免疫细胞的代谢活动，从而影响其分化和功能。通过探索免疫细胞在这一环境中的代谢需求，未来的研究有望为癌症治疗提供新的策略。

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免疫学 · 免疫代谢学 · 体外模型 · 代谢 · 代谢组学

摘要 ​

免疫细胞的代谢影响其分化和功能。考虑到肿瘤微环境（TME）中环境因素的复杂相互作用可能对免疫、基质和肿瘤细胞类型的代谢活动产生深远影响，近年来人们对在TME中理解这些多样化代谢表型的兴趣日益增加。在这里，我们讨论了细胞外部对免疫细胞代谢活动的贡献。然后，考虑到实验系统和代谢谱技术的最新技术进展，我们提出了未来的研究方向，以更好地理解免疫细胞如何满足其在TME中的代谢需求，这可以为治疗带来益处。

英文摘要 ​

Immune cells' metabolism influences their differentiation and function. Given that a complex interplay of environmental factors within the tumor microenvironment (TME) can have a profound impact on the metabolic activities of immune, stromal, and tumor cell types, there is emerging interest to advance understanding of these diverse metabolic phenotypes in the TME. Here, we discuss cell-extrinsic contributions to the metabolic activities of immune cells. Then, considering recent technical advances in experimental systems and metabolic profiling technologies, we propose future directions to better understand how immune cells meet their metabolic demands in the TME, which can be leveraged for therapeutic benefit.

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主要研究问题 ​

  1. 在肿瘤微环境中，免疫细胞的代谢活动如何受到肿瘤细胞的影响？
  2. 不同类型的免疫细胞在肿瘤微环境中的代谢表型有何差异，这些差异对肿瘤进展有何影响？
  3. 环境因素如何调节免疫细胞的代谢，进而影响其功能和分化？
  4. 在肿瘤微环境中，代谢剖析技术如何帮助识别潜在的治疗靶点？
  5. 如何利用对免疫细胞代谢的理解来开发新的免疫疗法，以提高治疗效果？

核心洞察 ​

研究背景和目的 ​

肿瘤微环境(TME)中的免疫细胞代谢与其分化和功能密切相关。环境因素的复杂相互作用影响免疫、基质和肿瘤细胞的代谢活动，因此深入理解这些代谢表型的多样性对开发新型治疗策略具有重要意义。本文旨在探讨TME中免疫细胞的代谢如何受到外部因素的影响，并提出未来研究的方向。

主要方法/材料/实验设计 ​

本文采用了文献综述的方式，整合了多项研究结果，并提出了一种新颖的实验设计思路，以更好地理解TME中免疫细胞的代谢需求。以下是研究的技术路线图：

Mermaid diagram

关键结果和发现 ​

  1. 营养物质的可用性：免疫细胞（如T细胞和巨噬细胞）依赖葡萄糖和谷氨酰胺等营养物质来满足其代谢需求。葡萄糖的限制会削弱肿瘤浸润淋巴细胞的效应功能。
  2. 代谢产物的影响：乳酸、犬尿喹啉酸和腺苷等代谢废物对T细胞功能具有免疫调节作用。乳酸可抑制CD8+效应细胞的细胞毒性。
  3. 氧气和pH的作用：低氧环境会通过稳定HIF-1α影响免疫细胞的功能，而TME的酸性环境则会影响免疫细胞的代谢状态。
  4. 细胞间相互作用：TME中的免疫细胞、肿瘤细胞和基质细胞之间的相互作用会影响代谢特征，进而影响抗肿瘤免疫反应。

主要结论/意义/创新性 ​

研究表明，TME中免疫细胞的代谢特征是由多种细胞内外因素共同决定的。通过整合生理培养基、稳定同位素追踪和三维培养模型等新技术，未来可以更深入地研究免疫细胞的代谢，并利用这些知识开发针对癌症的个性化治疗策略。

研究局限性和未来方向 ​

  1. 局限性：现有研究大多基于细胞培养模型，可能无法完全反映体内真实的TME代谢环境。
  2. 未来方向：需要进一步探索不同类型肿瘤的TME代谢特征，开发更为精确的体内模型和临床试验，以验证代谢干预在癌症治疗中的有效性。此外，利用微生物组和饮食对代谢的影响也值得深入研究。

参考文献 ​

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  1. CRISPR screens in physiologic medium reveal conditionally essential genes in human cells. - Nicholas J Rossiter;Kimberly S Huggler;Charles H Adelmann;Heather R Keys;Ross W Soens;David M Sabatini;Jason R Cantor - Cell metabolism (2021)
  2. ATP2C2 Has Potential to Define Tumor Microenvironment in Breast Cancer. - Jiazhou Liu;Yuxian Wei;Yushen Wu;Jie Li;Jiazheng Sun;Guosheng Ren;Hongzhong Li - Frontiers in immunology (2021)
  3. Immunometabolism of Tissue-Resident Macrophages - An Appraisal of the Current Knowledge and Cutting-Edge Methods and Technologies. - Giulia Zago;Pedro H V Saavedra;Kayvan R Keshari;Justin S A Perry - Frontiers in immunology (2021)
  4. Metabolic Interplay between the Immune System and Melanoma Cells: Therapeutic Implications. - Alice Indini;Francesco Grossi;Mario Mandalà;Daniela Taverna;Valentina Audrito - Biomedicines (2021)
  5. IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment. - Kewei Liu;Ai Huang;Jun Nie;Jun Tan;Shijie Xing;Yue Qu;Ke Jiang - Frontiers in immunology (2021)
  6. Metabolic Interdependency of Th2 Cell-Mediated Type 2 Immunity and the Tumor Microenvironment. - Simon Schreiber;Christoph M Hammers;Achim J Kaasch;Burkhart Schraven;Anne Dudeck;Sascha Kahlfuss - Frontiers in immunology (2021)
  7. High SQLE Expression and Gene Amplification Correlates with Poor Prognosis in Head and Neck Squamous Cell Carcinoma. - Yang Liu;Lijun Fang;Weixian Liu - Cancer management and research (2021)
  8. Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy. - Miljana Nenkov;Yunxia Ma;Nikolaus Gaßler;Yuan Chen - International journal of molecular sciences (2021)
  9. The therapeutic implications of immunosuppressive tumor aerobic glycolysis. - Bradley I Reinfeld;W Kimryn Rathmell;Tae Kon Kim;Jeffrey C Rathmell - Cellular & molecular immunology (2022)
  10. Circadian regulation of cancer cell and tumor microenvironment crosstalk. - Wenjing Xuan;Fatima Khan;Charles David James;Amy B Heimberger;Maciej S Lesniak;Peiwen Chen - Trends in cell biology (2021)

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