Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend?

Abstract

The major concept of "oxidative stress" is an excess elevated level of reactive oxygen species (ROS) which are generated from vigorous metabolism and consumption of oxygen. The precise harmonization of oxidative stresses between mitochondria and other organelles in the cell is absolutely vital to cell survival. Under oxidative stress, ROS produced from mitochondria and are the major mediator for tumorigenesis in different aspects, such as proliferation, migration/invasion, angiogenesis, inflammation, and immunoescape to allow cancer cells to adapt to the rigorous environment. Accordingly, the dynamic balance of oxidative stresses not only orchestrate complex cell signaling events in cancer cells but also affect other components in the tumor microenvironment (TME). Immune cells, such as M2 macrophages, dendritic cells, and T cells are the major components of the immunosuppressive TME from the ROS-induced inflammation. Based on this notion, numerous strategies to mitigate oxidative stresses in tumors have been tested for cancer prevention or therapies; however, these manipulations are devised from different sources and mechanisms without established effectiveness. Herein, we integrate current progress regarding the impact of mitochondrial ROS in the TME, not only in cancer cells but also in immune cells, and discuss the combination of emerging ROS-modulating strategies with immunotherapies to achieve antitumor effects.

Ovarian Cancer: A Landscape of Mitochondria with Emphasis on Mitochondrial Dynamics

“…Metabolic reprogramming supports cancer cell proliferation, survival, migration, and invasion. Moreover, ROS produced by mitochondrial metabolism and nutrient availability are important for interaction with cancer microenvironment components [ 44 ].…”

“…Several aspects have been found altered in cancer cells, such as mtDNA mutation, mitochondria-nuclear communication, oxidative stress, cell apoptosis, autophagy, dynamics and calcium overload [ 38 , 39 , 40 ]. To sustain cell proliferation, the cancer cells acquire the ability to change their metabolism equilibrating both glycolysis and OXPHOS for ATP production [ 43 , 44 ].…”

Dysbiosis: The first hit for digestive system cancer

“…Autophagy ( Onorati et al, 2018 ; Li et al, 2020 ) and oxidative stress ( Greenwood and Witney, 2021 ; Kuo et al, 2022 ) are cancer-related cellular stress responses. Autophagy refers to a series of mechanisms that transport superfluous or potentially dangerous cytoplasmic entities to the lysosome for degradation.…”

Recent Advances in the Development of Oxidoreductase-Based Biosensors for Detection of Phenolic Antioxidants in Food and Beverages

“…At low to moderate concentrations, ROS can function as a cellular signaling messenger; however, at high concentrations, these highly reactive species attack different biomolecules like proteins, carbohydrates, nucleic acids, fats, etc. present in the cells. , The outcome of severe oxidative damage to these biomolecules leads to the increment in the risk for the development of life-threatening diseases like cardiovascular disease, cancer, etc. in humans .…”

“…present in the cells. 1 , 2 The outcome of severe oxidative damage to these biomolecules leads to the increment in the risk for the development of life-threatening diseases like cardiovascular disease, cancer, etc. in humans.…”