Blocking inflammation to improve immunotherapy of advanced cancer. Issue 4 (27th December 2019)

• Record Type: Journal Article
• Authors: Macciò, Antonio; Madeddu, Clelia
• Is Part Of: Immunology. Volume 159:Issue 4(2020)
• Page Start: 357
• Page End: 364
• Publication Date: 2019-12-27
• Subjects: immunotherapy -- inflammation -- macrophages -- regulatory T cells -- tumor immunology; Immunology -- Periodicals
• DOI: 10.1111/imm.13164
• Languages: English
• ISSNs: 0019-2805

Abstract

Abstract: The ability to induce functional reprogramming of regulatory T (Treg) cells in the tumor microenvironment is an extremely important therapeutic opportunity. However, when discussing such an approach, the opposing effect that the activation of the Treg cell compartments may have in inducing the immune inflammatory response and its link with the efficacy of immunotherapy should be considered. In fact, Treg reprogramming has a dual effect: immediate, with mechanisms that activate immunosurveillance, and late, mediated by the macrophage activation that yields an inflammatory status that is deleterious for the antineoplastic efficiency of the immune system response. Persistence of the inflammatory response is associated with specific changes of oxidative and glycolytic metabolic pathways that interfere with conventional T‐cell activation and function and may be one of the reasons for the failure of immunotherapy in advanced cancer patients. Therefore, in addition to modulating Treg cell action, the combined use of drugs able to block chronic inflammation mediated mainly by macrophages, to counteract the oxidative stress, and to positively regulate the metabolic derangements, could improve the effectiveness of modern immunotherapy. In conclusion, reprogramming of Treg cells may be an appropriate strategy for treating early stages of neoplastic diseases, whereas other immunosuppressive mechanisms should be the target of a combined immunotherapy approach in more advanced phases of cancer. Abstract : The ability to induce functional reprogramming of regulatory T (Treg) cells in the tumor microenvironment is an extremely important therapeutic opportunity. However, Treg reprogramming stimulates counter‐regulatory mechanisms inducing an inflammatory status deleterious for the antineoplastic efficiency of the immune system response Therefore, a combined approach, with drugs that modulate chronic inflammation, counteracting oxidative stress and correcting derangements of energy and iron metabolism, could optimize the efficacy of Treg reprogramming in the context of modern cancer immunotherapy.