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Review
. 2024;31(31):4958-4986.
doi: 10.2174/0929867331666230719142202.

Does each Component of Reactive Oxygen Species have a Dual Role in the Tumor Microenvironment?

Siyu Hao  1   2 , Dan Cai  1   2   3 , Shuang Gou  1   2 , Yan Li  1 , Lin Liu  1   2   3 , Xiaolong Tang  1   2 , Yu Chen  1   2   3 , Yueshui Zhao  1   2   3 , Jing Shen  1   2   3 , Xu Wu  1   2   3 , Mingxing Li  1   2   3 , Meijuan Chen  1   1 , Xiaobing Li  1 , Yuhong Sun  1 , Li Gu  1 , Wanping Li  1 , Fang Wang  1 , Chi Hin Cho  1   4 , Zhangang Xiao  1   2   3   5 , Fukuan Du  1   2   3
Affiliations
Review

Does each Component of Reactive Oxygen Species have a Dual Role in the Tumor Microenvironment?

Siyu Hao et al. Curr Med Chem. 2024.

Abstract

Reactive oxygen species (ROS) are a class of highly reactive oxidizing molecules, including superoxide anion (O2 •-) and hydrogen peroxide (H2O2), among others. Moderate levels of ROS play a crucial role in regulating cellular signaling and maintaining cellular functions. However, abnormal ROS levels or persistent oxidative stress can lead to changes in the tumor microenvironment (TME) that favor cancer development. This review provides an overview of ROS generation, structure, and properties, as well as their effects on various components of the TME. Contrary to previous studies, our findings reveal a dual effect of ROS on different components of the TME, whereby ROS can either enhance or inhibit certain factors, ultimately leading to the promotion or suppression of the TME. For example, H2O2 has dual effects on immune cells and non-- cellular components within the TME, while O2 •- has dual effects on T cells and fibroblasts. Furthermore, each component demonstrates distinct mechanisms of action and ranges of influence. In the final section of the article, we summarize the current clinical applications of ROS in cancer treatment and identify certain limitations associated with existing therapeutic approaches. Therefore, this review aims to provide a comprehensive understanding of ROS, highlighting their dual effects on different components of the TME, and exploring the potential clinical applications that may pave the way for future treatment and prevention strategies.

Keywords: ROS; metabolism; microenvironment; molecule; therapy.; tumor.

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Conflict of interest statement

The authors declare no conflict of interest, financial or otherwise.

Figures

Fig. (1)
Fig. (1)
Describes the components of TME and the relationship between various components. TME mainly includes immune cells, stromal cells, and non-cellular components such as ECM. The components of TME coordinate with each other and are closely related.
Fig. (2)
Fig. (2)
Describes the ROS formation pathway in the body. The superoxide anion is mainly produced in complex I and complex III in mitochondria and relies on NADPH enzymosomes to transfer hydrogen. Hydrogen peroxide is mainly produced by superoxide anion catalyzed by SOD or by electron transfer from ERO1 and PDI enzymes of the endoplasmic reticulum to molecular oxygen. Hydrogen peroxide further undergoes the Fenton and Haber reactions to produce hydroxyl peroxyl. Phagocytic cells, the MPO, and the EPO systems produce singlet oxygen. The four ROS components are not produced independently but have a cascade relationship.
Fig. (3)
Fig. (3)
The effect of each component of ROS on the TME component.
Fig. (4)
Fig. (4)
Depicts the change of ROS effect on TME with the change of ROS level. At low concentrations, ROS mainly plays a role in signal transduction. With the occurrence of the tumor, ROS promotes tumor invasion and metastasis, proliferation, and mitochondrial damage. When the concentration of ROS reached a certain level, the apoptosis and DNA damage of cells in the TME environment were induced more. The graph shows existing treatment strategies for this condition. In addition, future research directions are proposed based on the relationship between ROS and TME.
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