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文献精选 > 高引权威"肿瘤微环境"文献

The tumor microenvironment. ​

文献信息 ​

DOI10.1016/j.cub.2020.06.081
PMID32810447
期刊Current biology : CB
影响因子7.5
JCR 分区Q1
发表年份2020
被引次数1172
关键词肿瘤微环境, 免疫细胞, 血管生成, 肿瘤进展
文献类型Journal Article
ISSN0960-9822
页码R921-R925
期号30(16)
作者Nicole M Anderson, M Celeste Simon

一句话小结 ​

本研究揭示了肿瘤微环境的复杂性及其在癌症进展中的关键角色，强调肿瘤不仅由癌细胞构成，还包括多种宿主细胞及其分泌因子，这些成分通过动态相互作用支持肿瘤生长。研究意义在于为未来癌症治疗提供新的干预靶点，推动相关治疗策略的开发。

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肿瘤微环境 · 免疫细胞 · 血管生成 · 肿瘤进展

摘要 ​

肿瘤不仅仅是一群癌细胞，而是一个异质性的集合，包括浸润性和驻留的宿主细胞、分泌因子及细胞外基质。肿瘤细胞刺激宿主组织内显著的分子、细胞和物理变化，以支持肿瘤的生长和进展。新兴的肿瘤微环境是一个复杂且不断演变的实体。肿瘤微环境的组成因肿瘤类型而异，但其标志性特征包括免疫细胞、基质细胞、血管和细胞外基质。人们认为，“肿瘤微环境不仅仅是一个沉默的旁观者，而是癌症进展的积极促进者”（Truffi et al., 2020）。在肿瘤生长的早期，癌细胞与肿瘤微环境成分之间发展出一种动态的、相互作用的关系，这种关系支持癌细胞的存活、局部侵袭和转移扩散。为了克服缺氧和酸性微环境，肿瘤微环境协调一个促进血管生成的程序，以恢复氧气和营养供应并清除代谢废物。肿瘤中会浸润多种适应性和先天免疫细胞，这些细胞能够执行促肿瘤和抗肿瘤的双重功能（见图1）。关于肿瘤微环境的文献不断增加，已在其中识别出新的治疗干预靶点。

英文摘要 ​

A tumor is not simply a group of cancer cells, but rather a heterogeneous collection of infiltrating and resident host cells, secreted factors and extracellular matrix. Tumor cells stimulate significant molecular, cellular and physical changes within their host tissues to support tumor growth and progression. An emerging tumor microenvironment is a complex and continuously evolving entity. The composition of the tumor microenvironment varies between tumor types, but hallmark features include immune cells, stromal cells, blood vessels, and extracellular matrix. It is believed that the "tumor microenvironment is not just a silent bystander, but rather an active promoter of cancer progression" (Truffi et al., 2020). Early in tumor growth, a dynamic and reciprocal relationship develops between cancer cells and components of the tumor microenvironment that supports cancer cell survival, local invasion and metastatic dissemination. To overcome a hypoxic and acidic microenvironment, the tumor microenvironment coordinates a program that promotes angiogenesis to restore oxygen and nutrient supply and remove metabolic waste. Tumors become infiltrated with diverse adaptive and innate immune cells that can perform both pro- and anti- tumorigenic functions (Figure 1). An expanding literature on the tumor microenvironment has identified new targets within it for therapeutic intervention.

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主要研究问题 ​

  1. 肿瘤微环境中的免疫细胞如何影响肿瘤的进展和治疗反应？
  2. 不同类型的肿瘤微环境在结构和功能上有何显著差异？
  3. 在肿瘤微环境中，基质成分如何调节肿瘤细胞的生存和侵袭能力？
  4. 目前针对肿瘤微环境的治疗策略有哪些，它们的机制是什么？
  5. 如何评估肿瘤微环境对新型抗癌药物疗效的影响？

核心洞察 ​

研究背景和目的 ​

肿瘤微环境（TME）不仅仅是癌细胞的集合，而是由浸润和驻留的宿主细胞、分泌因子和细胞外基质组成的异质性集合体。研究表明，肿瘤微环境在肿瘤生长和进展中起着积极的促进作用。本文旨在深入探讨肿瘤微环境的组成、功能及其在癌症进展中的作用。

主要方法/材料/实验设计 ​

本研究通过文献回顾和综合分析，描述了肿瘤微环境中各类细胞及其相互作用。主要方法包括：

  • 分析肿瘤微环境中不同类型的细胞（如免疫细胞、基质细胞、内皮细胞等）的功能和作用。
  • 探讨细胞间的相互作用及其对肿瘤发展的影响。

以下是技术路线的流程图：

Mermaid diagram

关键结果和发现 ​

  • 免疫细胞：肿瘤微环境中的免疫细胞可以抑制或促进肿瘤生长。细胞毒性T细胞（CD8+）与良好预后相关，而调节性T细胞（Tregs）则通过抑制抗肿瘤免疫反应促进肿瘤进展。
  • 基质细胞：癌相关成纤维细胞在肿瘤微环境中通过分泌生长因子和细胞因子促进肿瘤的增殖和转移。巨噬细胞的M2型也有助于肿瘤生长。
  • 内皮细胞：内皮细胞在肿瘤血管生成中起关键作用，缺氧和代谢废物的积累刺激内皮细胞分泌促血管生成因子，如VEGF。

主要结论/意义/创新性 ​

肿瘤微环境是一个动态的、复杂的系统，各种细胞之间的相互作用对肿瘤的发生和发展具有重要影响。理解这些机制为开发新的治疗策略提供了可能，尤其是靶向肿瘤微环境的治疗方法。

研究局限性和未来方向 ​

  • 局限性：目前对肿瘤微环境的理解仍不够全面，尤其是在不同肿瘤类型之间的差异。
  • 未来方向：需要进一步研究不同细胞类型在肿瘤微环境中的具体作用及其机制，并探索新的靶向治疗策略，例如靶向癌相关成纤维细胞和内皮细胞的疗法。
研究方面发现
免疫细胞T细胞的不同亚群对肿瘤有不同影响
基质细胞癌相关成纤维细胞促进肿瘤进展
内皮细胞参与血管生成和肿瘤细胞转移
未来研究方向探索靶向肿瘤微环境的新疗法

参考文献 ​

  1. The Tumor Microenvironment Innately Modulates Cancer Progression. - Dominique C Hinshaw;Lalita A Shevde - Cancer research (2019)
  2. B cells, plasma cells and antibody repertoires in the tumour microenvironment. - George V Sharonov;Ekaterina O Serebrovskaya;Diana V Yuzhakova;Olga V Britanova;Dmitriy M Chudakov - Nature reviews. Immunology (2020)
  3. Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy. - Erik Henke;Rajender Nandigama;Süleyman Ergün - Frontiers in molecular biosciences (2019)
  4. Oxygen availability and metabolic reprogramming in cancer. - Hong Xie;M Celeste Simon - The Journal of biological chemistry (2017)
  5. Immunological hallmarks of stromal cells in the tumour microenvironment. - Shannon J Turley;Viviana Cremasco;Jillian L Astarita - Nature reviews. Immunology (2015)
  6. Fates of CD8+ T cells in Tumor Microenvironment. - Nomathamsanqa Resegofetse Maimela;Shasha Liu;Yi Zhang - Computational and structural biotechnology journal (2019)
  7. Tumor-associated stromal cells as key contributors to the tumor microenvironment. - Karen M Bussard;Lysette Mutkus;Kristina Stumpf;Candelaria Gomez-Manzano;Frank C Marini - Breast cancer research : BCR (2016)

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  2. The enteric nervous system in gastrointestinal disease etiology. - Amy Marie Holland;Ana Carina Bon-Frauches;Daniel Keszthelyi;Veerle Melotte;Werend Boesmans - Cellular and molecular life sciences : CMLS (2021)
  3. Oncoimmunology Meets Organs-on-Chip. - Fabrizio Mattei;Sara Andreone;Arianna Mencattini;Adele De Ninno;Luca Businaro;Eugenio Martinelli;Giovanna Schiavoni - Frontiers in molecular biosciences (2021)
  4. Next-Generation Digital Histopathology of the Tumor Microenvironment. - Felicitas Mungenast;Achala Fernando;Robert Nica;Bogdan Boghiu;Bianca Lungu;Jyotsna Batra;Rupert C Ecker - Genes (2021)
  5. Tissue-Resident and Recruited Macrophages in Primary Tumor and Metastatic Microenvironments: Potential Targets in Cancer Therapy. - Tiziana Cotechini;Aline Atallah;Arielle Grossman - Cells (2021)
  6. 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)
  7. Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors. - Zhan Zhao;Hui Ding;Zheng-Bin Lin;Sheng-Hui Qiu;Yi-Ran Zhang;Yan-Guan Guo;Xiao-Dong Chu;Loi I Sam;Jing-Hua Pan;Yun-Long Pan - International journal of medical sciences (2021)
  8. Imaging Extracellular Acidification and Immune Activation in Cancer. - Fahmeed Hyder;Daniel Coman - Current opinion in biomedical engineering (2021)
  9. Application of Nano-Drug Delivery System Based on Cascade Technology in Cancer Treatment. - Ying Sun;Xiaoli Ma;Hao Hu - International journal of molecular sciences (2021)
  10. Pan-cancer characterization of lncRNA modifiers of immune microenvironment reveals clinically distinct de novo tumor subtypes. - Zicheng Zhang;Congcong Yan;Ke Li;Siqi Bao;Lei Li;Lu Chen;Jingting Zhao;Jie Sun;Meng Zhou - NPJ genomic medicine (2021)

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