Reactive Oxygen Species in the Tumor Microenvironment: An Overview
Open accessAbstract
Reactive oxygen species (ROS) are important signaling molecules in cancer. The level of ROS will determine physiological effects. While high levels of ROS can cause damage to tissues and cell death, low levels of ROS can have a proliferative effect. ROS are produced by tumor cells but also cellular components that make up the tumor microenvironment (TME). In this review, we discuss the mechanisms by which ROS can affect the TME with particular emphasis on tumor-infiltrating leukocytes. Greater insight into ROS biology in this setting may allow for therapeutic manipulation of ROS levels in order to remodel the tumor microenvironment and increase anti-tumor activity.
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The generation of ROS is increased in cancer cells compared to normal cells due to elevated energetic metabolic rates, gene mutations, and microenvironmental conditions such as hypoxia.
“The generation of ROS is increased in cancer cells compared to normal cells due to elevated energetic metabolic rates, gene mutations, and microenvironmental conditions such as hypoxia [68].”
From Chronic Inflammation, Oxidative Stress and Metabolic Plasticity: Three Players Driving the Pro-Tumorigenic Microenvironment in Malignant Mesothelioma (2023) · cites this paper as [68]
Section 2 reports elevated ROS in cancer cells and says oncogenes, tumor-suppressor loss, and mitochondrial DNA mutations can increase ROS production. Section 7 links metabolic reprogramming to subsequent ROS generation, but does not specifically identify elevated energetic metabolic rates as the cause. The hypoxia passage in Section 2 describes ROS helping stabilize HIF under hypoxia, not hypoxia increasing ROS generation. (LLM, conf=0.86)
Experimental — accuracy not yet measuredROS are highly chemically reactive molecules derived from deficient reduction in molecular oxygen and play a critical role as signaling molecules in tumorigenesis, including asbestos-mediated carcinogenesis.
“ROS are highly chemically reactive molecules, derived from the deficient reduction in molecular oxygen (O2) and playing a critical role as signaling molecules in tumorigenesis [68], including asbestos-mediated carcinogenesis [15,66,69].”
From Chronic Inflammation, Oxidative Stress and Metabolic Plasticity: Three Players Driving the Pro-Tumorigenic Microenvironment in Malignant Mesothelioma (2023) · cites this paper as [68]
The tumor microenvironment creates a field with a high concentration of ROS.
“It is well documented that the TME, comprised of many different cell types, such as cancer cells, cancer‐associated fibroblasts and numerous immune cells, creates a field with a high concentration of ROS.63”
From Reactive Oxygen Species in Cancer: Current Findings and Future Directions (2021) · cites this paper as [63]
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“The generation of ROS is increased in c ncer cells compared to ormal cells due to elevated energetic metabolic rates, gene mutatio s, and microenvironmental conditions such as hypoxia [68].”
BackgroundInfluentialOptimized indocyanine green nanopreparations for biomedical applications
Xia, W.-L., Ran, X.-Y., Xie, K.-P., Zhao, Y., Chen, J., Zhou, Q., Yu, X.-Q., & Li, K. (2025) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2024.216422 · Cited by 33 · see citing works
- Authors
- Weinberg, F., Ramnath, N., & Nagrath, D.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Nagrath, Deepak
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2019-08-16
- Volume
- 11
- Issue
- 8
- Pages
- 1191
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC6721577
- OpenAlex
- W2967873149
- Cited by
- 502
- References
- 156
- Citations by year
- 2026: 59 · 2025: 75 · 2024: 63 · 2023: 85 · 2022: 74 · 2021: 93 · 2020: 50 · 2019: 3
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R01CA204969, R01CA227622)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- reactive oxygen species, tumor microenvironment, tumor-infiltrating leukocytes, ROS signaling, tumor cell proliferation, oxidative stress, antitumor immunity
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