The Involvement of IL-17 – ACE-ACE2 System Connections in the Pathogenesis of Cancer

Until few years ago, TGF-beta was considered one of the main pro-tumoral endogenous molecules, because of its immunosuppressive activity, due to an inhibitory effect on the secretion of both IL-2 and IL-12, the two major anticancer cytokines in humans.IL-17, which was considered the main cytokine responsible for the pathogenesis of the autoimmune diseases because of its inhibitory action on T reg cells and TGF-beta secretion, has recently appeared to play a major pro-tumoral role, due to several mechanisms, including a direct stimulation of cancer cell proliferation, neo-angiogenesis and macrophage system-induced immunosuppression of the anticancer immunity.Moreover, IL-17 has also appeared to induce an unbalanced ACE-to-ACE2 ratio by stimulating ACE expression, which in addition to its hypertensive action has been proven to exert inflammatory, pro-fibrotic and pro-tumoral effects, whereas ACE2 expression plays hypotensive, anti-inflammatory, anti-fibrotic and antitumoral antiproliferative properties.Therefore, the inhibition of IL-17 secretion and activity could constitute a new way in cancer therapy.At present, it is known that IL-17 secretion may be physiologically inhibited by IL-2, IL-12, and even though in a less manner by cannabinoid agonists and the pineal hormone melatonin.On the same way, anti-IL-17 monoclonal antibodies may also block IL-17 secretion.Therefore, the antitumor therapy with anti-IL-17 monoclonal antibodies might represent a new strategy in cancer immunotherapy.In addition, IL-2 cancer immunotherapy could be reintroduced in the clinical oncology with a new ratio, that of suppressing IL-17 secretion and/or activity.