Role of Arginase 1 and Nitric Oxide Synthase 2 as enzymatic mediators of the immunosuppressive activity in tumor-infiltrating myeloid derived suppressor cells

摘要: MDSCs (myeloid derived suppressor cells) are one of the most important immunoregulatory populations involved in generation a permissive environment allowing tumor escape, progression and spreading. In physiologic conditions protect organism from exacerbated immune responses order to surrounding tissues damage. During growth, cancer cells produce TDSFs (tumor soluble factors), which induce MDSC accumulation their acquisition persistent suppressive activity. Among several mechanisms exploited by exert function, L-arginine metabolism seems be fundamental for alteration microenvironment T effector cell dysfunctions. This work highlights vivo requirement ARG1 NOS2 biology during development. known phenotypic functional complexity. It is clear that many factors can shape identity function: here we show, indeed “educate” them progressively. We illustrate MDSC-mediated suppression but also expansion subsets MDSCs. mediated these enzymes crucial spreading metastasis, as depletion either enzyme produces 50-75% reduction number lung metastases. Finally, show effects novel drug AT38 ARG1/NOS2 sufficient improve ACT (adoptive therapy) therapeutic approaches. Data produced represent body evidence could improving efficiency anti-cancer therapies, identifies key targets restoring responses.