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Antioxidants
Special Issues
Role of Reactive Oxygen Species (ROS) in Tumor Microenvironment Modulation
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Role of Reactive Oxygen Species (ROS) in Tumor Microenvironment Modulation

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: 31 December 2025 | Viewed by 1017

Special Issue Editors

Dr. Antonis Giakountis

E-Mail Website
Guest Editor
Laboratory of Molecular Biology and Genomics, Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece
Interests: lncRNA-mediated transcriptional regulation; RNA–chromatin interactions; chromatin architecture; transcriptional and epigenetic regulation in cancer
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Dimitrios Kouretas

E-Mail Website
Guest Editor
Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece
Interests: antioxidant activity; plant phenolics; exercise; functional foods; toxicology; redox nutrition; antioxidant administration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Accumulating evidence indicates that the activation or suppression of specific genes leads to an alteration of reactive oxygen species (ROS) levels; this can act as a double-edged sword, mediating tumor suppressive or pro-oncogenic functions, depending on the specific biological context. Thus, a better understanding of the mechanisms that control such genes functions and the most appropriate context of their activation or suppression is a prerequisite for the development of effective therapeutic strategies.

This Special Issue focuses on how ROS levels influence the tumor microenvironment and cancer progression. In this respect, we welcome functional genomics studies that utilize spatial transcriptomics, single-cell sequencing and/or bulk deep sequencing to analyze gene expression changes in tumor-associated stromal cells in response to varying levels of ROS, identifying key signaling pathways, antitumor mechanisms, diagnostic/prognostic biomarkers and potential therapeutic targets for modulating oxidative stress in the tumor microenvironment.

Dr. Antonis Giakountis
Prof. Dr. Dimitrios Kouretas
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • reactive oxygen species
  • tumor microenvironment
  • stroma cells
  • functional genomics
  • spatial transcriptomics
  • single-cell sequencing
  • RNA-seq
  • cancer
  • diagnosis and prognosis
  • biomarkers

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Published Papers (2 papers)

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18 pages, 4946 KiB  
Article
Oxidative Stress by H2O2 as a Potential Inductor in the Switch from Commensal to Pathogen in Oncogenic Bacterium Fusobacterium nucleatum
by Alessandra Scano, Sara Fais, Giuliana Ciappina, Martina Genovese, Barbara Granata, Monica Montopoli, Pierluigi Consolo, Patrizia Carroccio, Paola Muscolino, Alessandro Ottaiano, Alessia Bignucolo, Antonio Picone, Enrica Toscano, Germano Orrù and Massimiliano Berretta
Antioxidants 2025, 14(3), 323; https://doi.org/10.3390/antiox14030323 - 7 Mar 2025
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Abstract
Background: Fusobacterium nucleatum is a pathobiont that plays a dual role as both a commensal and a pathogen. The oral cavity typically harbors this anaerobic, Gram-negative bacterium. At the same time, it is closely linked to colorectal cancer due to its potential involvement [...] Read more.
Background: Fusobacterium nucleatum is a pathobiont that plays a dual role as both a commensal and a pathogen. The oral cavity typically harbors this anaerobic, Gram-negative bacterium. At the same time, it is closely linked to colorectal cancer due to its potential involvement in tumor progression and resistance to chemotherapy. The mechanism by which it transforms from a commensal to a pathogen remains unknown. For this reason, we investigated the role of oxidative status as an initiatory factor in changing the bacterium’s pathogenicity profile. Methods: A clinical strain of F. nucleatum subsp. animalis biofilm was exposed to different oxidative stress levels through varying subinhibitory amounts of H2O2. Subsequently, we investigated the bacterium’s behavior in vitro by infecting the HT-29 cell line. We evaluated bacterial colonization, volatile sulfur compounds production, and the infected cell’s oxidative status by analyzing HMOX1, pri-miRNA 155, and 146a gene expression. Results: The bacterial colonization rate, dimethyl sulfide production, and pri-miRNA 155 levels all increased when stressed bacteria were used, suggesting a predominant pathogenic function of these strains. Conclusions: The response of F. nucleatum to different oxidative conditions could potentially explain the increase in its pathogenic traits and the existence of environmental factors that may trigger the bacterium’s pathogenicity and virulence. Full article
(This article belongs to the Special Issue Role of Reactive Oxygen Species (ROS) in Tumor Microenvironment Modulation)
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Review

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25 pages, 1135 KiB  
Review
Targeting Redox Signaling Through Exosomal MicroRNA: Insights into Tumor Microenvironment and Precision Oncology
by Moon Nyeo Park, Myoungchan Kim, Soojin Lee, Sojin Kang, Chi-Hoon Ahn, Trina Ekawati Tallei, Woojin Kim and Bonglee Kim
Antioxidants 2025, 14(5), 501; https://doi.org/10.3390/antiox14050501 - 22 Apr 2025
Abstract
Reactive oxygen species (ROS) play a dual role in cancer progression, acting as both signaling molecules and drivers of oxidative damage. Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that [...] Read more.
Reactive oxygen species (ROS) play a dual role in cancer progression, acting as both signaling molecules and drivers of oxidative damage. Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that modulates immune responses, angiogenesis, and therapeutic resistance. In particular, oxidative stress not only stimulates exosome biogenesis but also influences the selective packaging of redox-sensitive miRNAs (miR-21, miR-155, and miR-210) via RNA-binding proteins such as hnRNPA2B1 and SYNCRIP. These miRNAs, delivered through exosomes, alter gene expression in recipient cells and promote tumor-supportive phenotypes such as M2 macrophage polarization, CD8+ T-cell suppression, and endothelial remodeling. This review systematically explores how this ROS–miRNA–exosome axis orchestrates communication across immune and stromal cell populations under hypoxic and inflammatory conditions. Particular emphasis is placed on the role of NADPH oxidases, hypoxia-inducible factors, and autophagy-related mechanisms in regulating exosomal output. In addition, we analyze the therapeutic relevance of natural products and herbal compounds—such as curcumin, resveratrol, and ginsenosides—which have demonstrated promising capabilities to modulate ROS levels, miRNA expression, and exosome dynamics. We further discuss the clinical potential of leveraging this axis for cancer therapy, including strategies involving mesenchymal stem cell-derived exosomes, ferroptosis regulation, and miRNA-based immune modulation. Incorporating insights from spatial transcriptomics and single-cell analysis, this review provides a mechanistic foundation for the development of exosome-centered, redox-modulating therapeutics. Ultimately, this work aims to guide future research and drug discovery efforts toward integrating herbal medicine and redox biology in the fight against cancer. Full article
(This article belongs to the Special Issue Role of Reactive Oxygen Species (ROS) in Tumor Microenvironment Modulation)
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