Abstract
Reactive oxygen species (ROS) are critical mediators in many physiological processes including innate and adaptive immunity, making the modulation of ROS level a powerful strategy to augment anticancer immunity. However, current evidences suggest the necessity of a deeper understanding of their multiple roles, which may vary with their concentration, location and the immune microenvironment they are in. Here, we have reviewed the reported effects of ROS on macrophage polarization, immune checkpoint blocking (ICB) therapy, T cell activation and expansion, as well as the induction of immunogenic cell death. A majority of reports are indicating detrimental effects of ROS, but it is unadvisable to simply scavenge them because of their pleiotropic effects in most occasions (except in T cell activation and expansion where ROS are generally undesirable). Therefore, clinical success will need a clearer illustration of their multi-faced functions, as well as more advanced technologies to tune ROS level with high spatiotemporal control and species-specificity. With such progresses, the efficacy of current immunotherapies will be greatly improved by combining with ROS-targeted therapies.
Highlights
Reactive oxygen species (ROS) are a class of highly reactive oxygen-derived chemicals, including hydroxyl radical (·OH), singlet oxygen (1O2), superoxide anion (O2·−), and peroxides
ROS level in tumoral and lymphatic cells might be a potential indicator of the responsiveness to programmed death-1 (PD-1)/PD-L1 blockade therapy, especially considering that the expression of immune checkpoints has been accepted as a tumor-intrinsic sign of the vulnerability of tumors to immune checkpoint blocking (ICB) therapy (Zappasodi et al, 2018)
Studies directly exploring the effect of ROS on Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) therapy are rare to the best of our knowledge, but ROS have an obvious influence on the development of T regulatory cells (Tregs), on which CTLA-4 is constitutively expressed (Walker 2013)
Summary
Reactive oxygen species (ROS) are a class of highly reactive oxygen-derived chemicals, including hydroxyl radical (·OH), singlet oxygen (1O2), superoxide anion (O2·−), and peroxides. This review summarizes recent studies reporting ROS-mediated enhancement or attenuation of antitumor immunity, with an expectation of providing basic rationales for improved immunotherapy. Iron overload, which rapidly induced ROS production, polarized macrophages to pro-inflammatory phenotype, enhanced the activity of p300/CBP acetyltransferase and improved p53 acetylation (Zhou et al, 2018).
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