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The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth.
Literature Information
| DOI | 10.1016/j.ccell.2023.02.016 |
|---|---|
| PMID | 36917948 |
| Journal | Cancer cell |
| Impact Factor | 44.5 |
| JCR Quartile | Q1 |
| Publication Year | 2023 |
| Times Cited | 1317 |
| Keywords | tumor microenvironment, cancer progression, metastatic dissemination |
| Literature Type | Journal Article, Review, Research Support, Non-U.S. Gov't |
| ISSN | 1535-6108 |
| Pages | 374-403 |
| Issue | 41(3) |
| Authors | Karin E de Visser, Johanna A Joyce |
TL;DR
This paper reviews the tumor microenvironment (TME), highlighting its critical role in cancer progression through its diverse cellular composition and interactions with tumor cells. Understanding these complexities is essential for developing effective anti-cancer therapies tailored to specific tumor characteristics and patient factors.
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tumor microenvironment · cancer progression · metastatic dissemination
Abstract
Cancers represent complex ecosystems comprising tumor cells and a multitude of non-cancerous cells, embedded in an altered extracellular matrix. The tumor microenvironment (TME) includes diverse immune cell types, cancer-associated fibroblasts, endothelial cells, pericytes, and various additional tissue-resident cell types. These host cells were once considered bystanders of tumorigenesis but are now known to play critical roles in the pathogenesis of cancer. The cellular composition and functional state of the TME can differ extensively depending on the organ in which the tumor arises, the intrinsic features of cancer cells, the tumor stage, and patient characteristics. Here, we review the importance of the TME in each stage of cancer progression, from tumor initiation, progression, invasion, and intravasation to metastatic dissemination and outgrowth. Understanding the complex interplay between tumor cell-intrinsic, cell-extrinsic, and systemic mediators of disease progression is critical for the rational development of effective anti-cancer treatments.
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Primary Questions Addressed
- How do different immune cell types within the tumor microenvironment influence the efficacy of immunotherapy in various cancer types?
- What specific roles do cancer-associated fibroblasts play in the transition from tumor initiation to metastatic outgrowth?
- How does the extracellular matrix composition vary between different stages of cancer progression, and what implications does this have for treatment strategies?
- In what ways do patient characteristics, such as genetics and lifestyle, affect the tumor microenvironment and its impact on cancer progression?
- What are the latest findings on the systemic mediators that influence the tumor microenvironment and their potential as therapeutic targets?
Key Findings
Key Insights
Research Background and Objective
The study investigates the tumor microenvironment (TME), a complex ecosystem composed of tumor cells and a variety of non-cancerous cells, including immune cells, fibroblasts, endothelial cells, and pericytes, all embedded within an altered extracellular matrix. Traditionally viewed as passive participants in tumorigenesis, these host cells are now recognized for their significant roles in cancer pathogenesis. The objective of this review is to elucidate the dynamic role of the TME throughout different stages of cancer progression, from initiation to metastatic outgrowth, highlighting the intricate relationships and interactions that occur within this environment.Main Methods and Findings
The authors conducted a comprehensive review of existing literature to analyze the cellular composition and functional states of the TME across various cancer types and stages. They found that the TME is not homogenous; its composition and activity vary significantly depending on factors such as the organ of origin, the intrinsic characteristics of the cancer cells, the stage of tumor development, and the individual patient's biological context. The review underscores the importance of immune cell types and other resident non-cancerous cells in influencing tumor behavior and response to therapies. Key findings indicate that specific TME components can promote tumor growth, facilitate invasion and metastasis, and alter therapeutic responses.Core Conclusions
The review concludes that the TME plays a pivotal role in every phase of cancer progression, from the initial tumor formation to the eventual spread and outgrowth of metastases. The interactions between tumor cells and their microenvironment are critical determinants of tumor behavior and patient outcomes. Understanding these interactions provides insights into how the TME can be modulated to enhance the efficacy of existing and emerging anti-cancer therapies.Research Significance and Impact
This research is significant as it shifts the focus from cancer cells alone to the broader context of the TME, emphasizing its importance in cancer biology. By unraveling the complex interplay between tumor-intrinsic factors and the extrinsic influences of the TME, the findings pave the way for developing targeted therapies that can disrupt these interactions. The insights gained from this study could lead to innovative treatment strategies that consider the tumor ecosystem as a whole, ultimately improving patient outcomes and personalizing cancer treatment approaches. The recognition of the TME's role also challenges researchers and clinicians to rethink existing paradigms in cancer therapy, advocating for a more integrative approach in combating cancer.
Literatures Citing This Work
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