Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Feb:151:155747.
doi: 10.1016/j.metabol.2023.155747. Epub 2023 Nov 30.

The role of ROS in tumor infiltrating immune cells and cancer immunotherapy

Rushil Shah  1 , Betul Ibis  1 , Monisha Kashyap  1 , Vassiliki A Boussiotis  2
Affiliations
Review

The role of ROS in tumor infiltrating immune cells and cancer immunotherapy

Rushil Shah et al. Metabolism. 2024 Feb.

Abstract

Reactive oxygen species (ROS) are a group of short-lived highly reactive molecules formed intracellularly from molecular oxygen. ROS can alter biochemical, transcriptional, and epigenetic programs and have an indispensable role in cellular function. In immune cells, ROS are mediators of specialized functions such as phagocytosis, antigen presentation, activation, cytolysis, and differentiation. ROS have a fundamental role in the tumor microenvironment (TME) where they are produced by immune cell-intrinsic and -extrinsic mechanisms. ROS can act as a double-edged sword with short exposures leading to activation in various innate and adaptative immune cells, and prolonged exposures, unopposed by redox balancing antioxidants leading to exhaustion, immunosuppression, and unresponsiveness to cancer immunotherapy. Due to its plasticity and impact on the anti-tumor function of immune cells, attempts are currently in process to harness ROS biology with the purpose to improve contemporary strategies of cancer immunotherapy. Here, we provide a short overview how ROS and various antioxidant systems impact on the function of innate and adaptive immune system cells with emphasis on the TME and immune-based therapies for cancer.

Keywords: Immune cells; Reactive oxygen species; cancer immunotherapy; cancer microenvironment.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest VAB has patents on the PD-1 pathway licensed by Bristol-Myers Squibb, Roche, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis and Dako. The authors declare no other competing interests.

Figures

Figure 1
Figure 1
(A) Mechanisms of cellular ROS production. (B) Electron transport chain at the inner mitochondrial membrane. (C) Assembly and activation of NADPH oxidase (NOX) at the plasma membrane (See text for details).
Figure 2
Figure 2
Effects of ROS on the function of immune cells in the TME (See text for details)
Figure 3
Figure 3
ROS in ICT and cell-based immunotherapy for cancer treatment. (A) Increase of mitochondrial activation blockade of the PD-1: PD-L1 pathway alone or in combination with the OXPHOS uncoupler FCCP. (B) Enhanced differentiation, expansion, and effector function of myeloid cells by abrogation of PD-1 signaling. (C) CAR-T cells overexpressing catalase (CAT), thioredoxin 1 (TXN1) or c-SH enhancers display improve longevity and anti-tumor function. (D) Implantation of a ROS-sensitive hydrogel in the TME expressing a photosensitizer (chlorin-e6) and an immunotherapeutic antibody (CD47) alter the function of TAMs and T cells and promotes anti-tumor immunity in cold tumors.
See this image and copyright information in PMC

References

    1. Sies H, Belousov VV, Chandel NS, Davies MJ, Jones DP, Mann GE, et al. Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology. Nat Rev Mol Cell Biol 2022;23:499–515. - PubMed
    1. Murphy MP, Bayir H, Belousov V, Chang CJ, Davies KJA, Davies MJ, et al. Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo. Nat Metab 2022;4:651–62. - PMC - PubMed
    1. Cortese-Krott MM, Koning A, Kuhnle GGC, Nagy P, Bianco CL, Pasch A, et al. The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine. Antioxid Redox Signal 2017;27:684–712. - PMC - PubMed
    1. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 2014;94:909–50. - PMC - PubMed
    1. D’Autréaux B, Toledano MB. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 2007;8:813–24. - PubMed