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Stromal Cells in the Tumor Microenvironment.
Literature Information
| DOI | 10.1007/978-3-319-78127-3_6 |
|---|---|
| PMID | 30155624 |
| Journal | Advances in experimental medicine and biology |
| JCR Quartile | Q2 |
| Publication Year | 2018 |
| Times Cited | 178 |
| Keywords | Cancer-associated fibroblast, Immunotherapy, Stromal immunology, Tumor microenvironment |
| Literature Type | Journal Article, Review |
| ISSN | 0065-2598 |
| Pages | 99-114 |
| Issue | 1060() |
| Authors | Alice E Denton, Edward W Roberts, Douglas T Fearon |
TL;DR
This research highlights the critical role of cancer-associated fibroblasts (CAFs) within the tumor microenvironment, demonstrating how they support cancer growth by modulating immune responses and promoting factors like angiogenesis and inflammation. The findings suggest that targeting CAF functions could enhance the efficacy of cancer immunotherapies, underscoring the importance of the tumor microenvironment in cancer treatment strategies.
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Cancer-associated fibroblast · Immunotherapy · Stromal immunology · Tumor microenvironment
Abstract
The tumor microenvironment comprises a mass of heterogeneous cell types, including immune cells, endothelial cells, and fibroblasts, alongside cancer cells. It is increasingly becoming clear that the development of this support niche is critical to the continued uncontrolled growth of the cancer. The tumor microenvironment contributes to the maintenance of cancer stemness and also directly promotes angiogenesis, invasion, metastasis, and chronic inflammation. In this chapter, we describe on the role of fibroblasts, specifically termed cancer-associated fibroblasts (CAFs), in the promotion and maintenance of cancers. CAFs have a multitude of effects on the growth and maintenance of cancer, and here we focus on their roles in modulating immune cells and responses; CAFs both inhibit immune cell access to the tumor microenvironment and inhibit their functions within the tumor. Finally, we describe the potential modulation of CAF function as an adjunct to bolster the effectiveness of cancer immunotherapies.
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Primary Questions Addressed
- How do cancer-associated fibroblasts (CAFs) interact with immune cells in the tumor microenvironment to influence cancer progression?
- What specific mechanisms do CAFs use to inhibit immune cell functions within tumors, and how can these be targeted therapeutically?
- In what ways can the modulation of CAFs enhance the effectiveness of existing cancer immunotherapies?
- How does the heterogeneity of stromal cells within the tumor microenvironment affect the overall tumor behavior and response to treatment?
- What role do other stromal cell types, such as endothelial cells and immune cells, play in supporting or opposing the functions of CAFs in tumors?
Key Findings
Key Insights
Research Background and Objective:
The tumor microenvironment (TME) is recognized as a complex and heterogeneous milieu that includes various cell types, such as immune cells, endothelial cells, fibroblasts, and cancer cells. This study aims to elucidate the critical roles of stromal cells, particularly cancer-associated fibroblasts (CAFs), in the development and maintenance of tumors. Understanding the interactions between CAFs and other components of the TME is vital for comprehending how they contribute to cancer progression and resistance to therapy.Main Methods and Findings:
The chapter discusses the multifaceted roles of CAFs in the TME, focusing on their influence on immune cells. It highlights how CAFs contribute to tumor growth by creating a supportive niche that fosters cancer stemness, stimulates angiogenesis, and enhances invasion and metastasis. Importantly, the research outlines how CAFs can inhibit the access and functionality of immune cells within the TME, effectively suppressing anti-tumor immune responses. This immunosuppressive role of CAFs is critical in understanding their contribution to tumor progression and therapy resistance.Core Conclusions:
The study concludes that CAFs play a pivotal role in shaping the TME to favor cancer progression. By modulating immune cell activity and access, CAFs create an environment that not only supports tumor growth but also actively contributes to the evasion of immune surveillance. The findings underscore the dual role of CAFs as both promoters of cancer and as potential targets for therapeutic intervention.Research Significance and Impact:
This research highlights the importance of targeting CAFs to enhance the efficacy of cancer immunotherapies. By understanding how CAFs modulate immune responses, researchers can develop strategies to disrupt their immunosuppressive activities, potentially leading to improved outcomes for cancer patients. The insights gained from this study contribute to a broader understanding of the TME's role in cancer biology and open new avenues for therapeutic strategies aimed at reprogramming CAFs to support rather than impede anti-tumor immunity. Ultimately, this research could lead to the development of more effective cancer treatments that leverage the intricate dynamics of the tumor microenvironment.
Literatures Citing This Work
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- Interplay Between LOX Enzymes and Integrins in the Tumor Microenvironment. - Pier Giorgio Amendola;Raphael Reuten;Janine Terra Erler - Cancers (2019)
- SARI suppresses colitis-associated cancer development by maintaining MCP-1-mediated tumour-associated macrophage recruitment. - Lei Dai;Yi Liu;Yuan Yin;Junshu Li;Zhexu Dong;Na Chen;Lin Cheng;Huiling Wang;Chao Fang;Yi Lin;Gang Shi;Hantao Zhang;Ping Fan;Xiaolan Su;Shuang Zhang;Yang Yang;Lie Yang;Wei Huang;Zongguang Zhou;Dechao Yu;Hongxin Deng - Journal of cellular and molecular medicine (2020)
- Gastric cancer-derived mesenchymal stromal cells trigger M2 macrophage polarization that promotes metastasis and EMT in gastric cancer. - Wei Li;Xu Zhang;Fenglei Wu;Ying Zhou;Zengtao Bao;Haining Li;Ping Zheng;Shaolin Zhao - Cell death & disease (2019)
- Modifying the Tumour Microenvironment: Challenges and Future Perspectives for Anticancer Plasma Treatments. - Angela Privat-Maldonado;Charlotta Bengtson;Jamoliddin Razzokov;Evelien Smits;Annemie Bogaerts - Cancers (2019)
- The Multifaceted Effects of Autophagy on the Tumor Microenvironment. - Rui Kang;Herbert Zeh;Michael Lotze;Daolin Tang - Advances in experimental medicine and biology (2020)
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- Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma. - Vera Petrova;Ihor Arkhypov;Rebekka Weber;Christopher Groth;Peter Altevogt;Jochen Utikal;Viktor Umansky - International journal of molecular sciences (2020)
- Clinical effects of apatinib mesylate for treatment of multiple brain micrometastases: Two case reports. - Jun-Hui Guo;Yuan-Yuan Wang;Jiang-Wei Zhang;Pei-Min Liu;Yan-Jun Hao;Hai-Rui Duan - World journal of clinical cases (2020)
- The tumor microenvironment and radiotherapy response; a central role for cancer-associated fibroblasts. - Marleen Ansems;Paul N Span - Clinical and translational radiation oncology (2020)
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