Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy

Abstract

It has been well-established that cancer cells are under constant oxidative stress, as reflected by elevated basal level of reactive oxygen species (ROS), due to increased metabolism driven by aberrant cell growth. Cancer cells can adapt to maintain redox homeostasis through a variety of mechanisms. The prevalent perception about ROS is that they are one of the key drivers promoting tumor initiation, progression, metastasis, and drug resistance. Based on this notion, numerous antioxidants that aim to mitigate tumor oxidative stress have been tested for cancer prevention or treatment, although the effectiveness of this strategy has yet to be established. In recent years, it has been increasingly appreciated that ROS have a complex, multifaceted role in the tumor microenvironment (TME), and that tumor redox can be targeted to amplify oxidative stress inside the tumor to cause tumor destruction. Accumulating evidence indicates that cancer immunotherapies can alter tumor redox to intensify tumor oxidative stress, resulting in ROS-dependent tumor rejection. Herein we review the recent progresses regarding the impact of ROS on cancer cells and various immune cells in the TME, and discuss the emerging ROS-modulating strategies that can be used in combination with cancer immunotherapies to achieve enhanced antitumor effects.

Curcumin Reduces Colorectal Cancer Cell Proliferation and Migration and Slows In Vivo Growth of Liver Metastases in Rats

“…It has also been demonstrated that curcumin reduces tumor invasion and metastatic growth by, for example, reducing the activity of matrix metalloproteinases (MMPs) 2 and 9, or blocking nuclear translocation of nuclear factor kappa B (NFκB) by inhibiting the inhibitor of kappaB kinase [ 11 , 12 , 13 ]. This molecular pathway is also involved in the prevention of liver damage after exposure to radiotherapy [ 16 ] by regulating oxidative stress damage and reducing the accumulation of reactive oxygen species, which are well known to contribute to tumor progression by promoting cell transformation, proliferation, and the survival of tumor cells [ 17 ].…”

Reactive oxygen species: Key players in the anticancer effects of apigenin?

“…The antioxidant effect of apigenin is displayed primarily in normal cells while it exhibits pro-oxidation activity in cancer cells. The higher metabolic activity and basal oxidative stress of tumor cells relative to normal cells may have promoted the prooxidant effect of apigenin in the former (Aboelella et al, 2021).…”

Microenvironmental Reactive Oxygen Species in Colorectal Cancer: Involved Processes and Therapeutic Opportunities

“…It is used by neutrophils and macrophages to destroy pathogens as wells as cancer cells. Besides, these ROS are also involved in the activation of T cells and NK cells [8].…”

“…ROS are also involved in one of the most accepted mechanisms leading to metastasis, the epithelial-tomesenchymal transition (EMT) [7]. On the other hand, ROS play an important role in the antitumoral immune response through the activation of inflammatory and immune cells such as T lymphocytes and natural killer (NK) cells [8].…”