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Curated Papers > High-impact authoritative literature on "tumor microenvironment"

The tumor microenvironment. ​

Literature Information ​

DOI10.1016/j.cub.2020.06.081
PMID32810447
JournalCurrent biology : CB
Impact Factor7.5
JCR QuartileQ1
Publication Year2020
Times Cited1172
Keywordstumor microenvironment, immune cells, angiogenesis
Literature TypeJournal Article
ISSN0960-9822
PagesR921-R925
Issue30(16)
AuthorsNicole M Anderson, M Celeste Simon

TL;DR ​

This research highlights that the tumor microenvironment is a dynamic and complex entity composed of various cells and extracellular components that actively promote cancer progression rather than merely supporting it. By understanding these interactions and the role of immune cells, the study identifies potential new therapeutic targets to enhance cancer treatment strategies.

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tumor microenvironment · immune cells · angiogenesis

Abstract ​

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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Primary Questions Addressed ​

  1. How do specific immune cell types within the tumor microenvironment influence cancer progression and treatment outcomes?
  2. What are the key molecular signaling pathways involved in the interaction between tumor cells and stromal components of the tumor microenvironment?
  3. In what ways can targeting the tumor microenvironment enhance the efficacy of existing cancer therapies?
  4. How does the heterogeneity of the tumor microenvironment affect the development of drug resistance in cancer treatment?
  5. What role does the extracellular matrix play in the mechanical properties of the tumor microenvironment and its impact on tumor invasion?

Key Findings ​

Research Background and Objectives ​

The tumor microenvironment (TME) is a complex ecosystem composed of cancer cells, immune cells, stromal cells, and extracellular matrix (ECM). It plays a crucial role in tumor growth and progression. This primer aims to summarize the key components and functions of the TME, highlighting the interactions between tumor cells and their microenvironment, and exploring potential therapeutic targets within this context.

Main Methods/Materials/Experimental Design ​

The study employs a comprehensive review of existing literature on the tumor microenvironment, focusing on various cell types and their roles. The analysis is structured around key cellular components, including immune cells (T cells, B cells, natural killer cells, macrophages, neutrophils, dendritic cells), stromal cells (fibroblasts, endothelial cells, adipocytes, stellate cells), and non-cellular components (extracellular matrix, exosomes).

Mermaid diagram

Key Results and Findings ​

  1. Immune Cells: The TME contains diverse immune cells that can have both pro-tumorigenic and anti-tumorigenic roles. For instance, cytotoxic T cells (CD8+) are generally associated with better prognoses, while regulatory T cells (Tregs) can promote tumor progression by suppressing anti-tumor immune responses.
  2. Stromal Cells: Stromal cells, particularly cancer-associated fibroblasts, are crucial in supporting tumor growth, angiogenesis, and immune modulation. They produce various growth factors and cytokines that facilitate tumor progression.
  3. Extracellular Matrix: The ECM provides structural support and is involved in signaling pathways that promote tumor invasion and metastasis. It serves as a reservoir for growth factors and cytokines.
  4. Exosomes: These microvesicles mediate communication between tumor cells and the surrounding stroma, influencing inflammation and tumor progression.

Main Conclusions/Significance/Innovativeness ​

The study underscores the importance of the tumor microenvironment as an active participant in cancer progression rather than a mere backdrop. Understanding the dynamic interactions within the TME opens avenues for novel therapeutic strategies, particularly in targeting specific cellular components to enhance treatment efficacy.

Research Limitations and Future Directions ​

  • Limitations: The complexity and heterogeneity of the TME present challenges in developing universally effective therapies. Current FDA-approved treatments targeting the TME have shown limited efficacy, and patient responses can vary widely.
  • Future Directions: Ongoing research is needed to identify biomarkers for predicting responses to therapies targeting the TME. Innovative approaches, such as combining immune checkpoint inhibitors with therapies targeting stromal components, may enhance treatment outcomes. Additionally, further exploration of the roles of exosomes and specific immune cell subsets in the TME could provide new therapeutic targets.

In summary, the tumor microenvironment is a critical player in cancer biology, influencing tumor behavior and patient outcomes. Future therapeutic strategies should consider the intricate interplay of its components to improve cancer treatment efficacy.

References ​

  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)

Literatures Citing This Work ​

  1. Lactate Metabolism in Breast Cancer Microenvironment: Contribution Focused on Associated Adipose Tissue and Obesity. - Andjelika Kalezic;Mirjana Udicki;Biljana Srdic Galic;Marija Aleksic;Aleksandra Korac;Aleksandra Jankovic;Bato Korac - International journal of molecular sciences (2020)
  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)

... (1162 more literatures)

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