The tumor microenvironment and its role in promoting tumor growth
Open accessAbstract
The tumor microenvironment is created by the tumor and dominated by tumor-induced interactions. Although various immune effector cells are recruited to the tumor site, their anti-tumor functions are downregulated, largely in response to tumor-derived signals. Infiltrates of inflammatory cells present in human tumors are chronic in nature and are enriched in regulatory T cells (T(reg)) as well as myeloid suppressor cells (MSC). Immune cells in the tumor microenvironment not only fail to exercise antitumor effector functions, but they are co-opted to promote tumor growth. Sustained activation of the NF-kappaB pathway in the tumor milieu represents one mechanism that appears to favor tumor survival and drive abortive activation of immune cells. The result is tumor escape from the host immune system. Tumor escape is accomplished through the activation of one or several molecular mechanisms that lead to inhibition of immune cell functions or to apoptosis of anti-tumor effector cells. The ability to block tumor escape depends on a better understanding of cellular and molecular pathways operating in the tumor microenvironment. Novel therapeutic strategies that emerge are designed to change the pro-tumor microenvironment to one favoring acute responses and potent anti-tumor activity.
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Tumor initiation and progression are not governed solely by genetic mutations but are significantly influenced by the dynamic interplay between tumor cells and their surrounding microenvironment.
“It is now widely accepted that tumor initiation and progression are not governed solely by genetic mutations but are significantly influenced by the dynamic interplay between tumor cells and their surrounding microenvironment.”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [20]
The Introduction says the tumor microenvironment exerts a key influence on tumor progression, and the Conclusions describe cellular interactions that support tumor growth. The paper also associates inflammation with tumor development, but the cited passages do not clearly establish that the microenvironment influences tumor initiation, as the sentence claims. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe tumor microenvironment comprises a complex network of cellular, acellular, and immune components.
“This surrounding landscape—referred to as the tumor microenvironment (TME)—comprises a complex network of cellular, acellular, and immune components [5,20,21].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [20]
Cancer-associated fibroblasts (CAFs) are a major cellular component of the tumor microenvironment in most solid cancers.
“Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers.”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Whiteside, 2008
CAFs comprise the majority of cell types within the TME, and their reciprocal interactions with cancer cells are well documented.
“CAFs comprise the majority of cell types within the TME, and their reciprocal interactions with cancer cells have been well documented (Whiteside, 2008; Hazlehurst et al., 2003; Karnoub et al., 2007).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Whiteside, 2008
Paracrine signals from cancer cells can recruit and activate CAFs within the TME.
“Accumulating evidence suggests that paracrine signals from cancer cells can both recruit and activate CAFs within the TME, and contribute to their activation (Whiteside, 2008; Liao et al., 2009; Orimo et al., 2005; Chung et al., 2006).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Whiteside, 2008
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pH-sensitive biomaterials for drug delivery
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TLR8 signaling enhances tumor immunity by preventing tumor‐induced T‐cell senescence
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Development and characterization of a microfluidic model of the tumour microenvironment
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Biomimetic Model of Tumor Microenvironment on Microfluidic Platform
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3D Bioprinting of Tumor Models for Cancer Research
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Assessing the future of solid tumor immunotherapy
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“This surrounding landscape—referred to as the tumor microenvironment (TME)—comprises a complex network of cellular, acellular, and immune components [5,20,21].”
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Immunotherapies targeting stimulatory pathways and beyond
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Preoperative Platelet to Albumin Ratio Predicts Outcome of Patients with Non-Small-Cell Lung Cancer
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Deep learning in digital pathology for personalized treatment plans of cancer patients
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- Authors
- Whiteside, T. L.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Whiteside, T L
- ORCID
- Whiteside, T L
- Venue
- Oncogene
- Published
- 2008-10-06
- Volume
- 27
- Issue
- 45
- Pages
- 5904-5912
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC3689267
- OpenAlex
- W2126882378
- Cited by
- 2,376
- References
- 85
- Citations by year
- 2026: 88 · 2025: 126 · 2024: 187 · 2023: 269 · 2022: 288 · 2021: 302 · 2020: 190 · 2019: 145 · 2018: 133 · 2017: 106 · 2016: 101 · 2015: 80 · 2014: 58 · 2013: 87 · 2012: 57
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p01ca109688-05)
- National Cancer Institute (P0-1 CA109688)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- tumor microenvironment, tumor growth, immune evasion, regulatory T cells, myeloid-derived suppressor cells, NF-κB signaling, tumor-infiltrating immune cells, antitumor immunity, immune checkpoint blockade, cancer immunotherapy
- MeSH terms
- Animals, Cell Communication, Humans, Immunotherapy, Inflammation, Models, Biological, Neoplasms, Tumor Escape, Extracellular Fluid, Tumor Burden, Cell Proliferation
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