TY - JOUR T1 - Thymosin α1 protects from CTLA-4 intestinal immunopathology JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202000662 VL - 3 IS - 10 SP - e202000662 AU - Giorgia Renga AU - Marina M Bellet AU - Marilena Pariano AU - Marco Gargaro AU - Claudia Stincardini AU - Fiorella D’Onofrio AU - Paolo Mosci AU - Stefano Brancorsini AU - Andrea Bartoli AU - Allan L Goldstein AU - Enrico Garaci AU - Luigina Romani AU - Claudio Costantini Y1 - 2020/10/01 UR - https://www.life-science-alliance.org/content/3/10/e202000662.abstract N2 - The advent of immune checkpoint inhibitors has represented a major boost in cancer therapy, but safety concerns are increasingly being recognized. Indeed, although beneficial at the tumor site, unlocking a safeguard mechanism of the immune response may trigger autoimmune-like effects at the periphery, thus making the safety of immune checkpoint inhibitors a research priority. Herein, we demonstrate that thymosin α1 (Tα1), an endogenous peptide with immunomodulatory activities, can protect mice from intestinal toxicity in a murine model of immune checkpoint inhibitor–induced colitis. Specifically, Tα1 efficiently prevented immune adverse pathology in the gut by promoting the indoleamine 2,3-dioxygenase (IDO) 1–dependent tolerogenic immune pathway. Notably, Tα1 did not induce IDO1 in the tumor microenvironment, but rather modulated the infiltration of T-cell subsets by inverting the ratio between CD8+ and Treg cells, an effect that may depend on Tα1 ability to regulate the differentiation and chemokine expression profile of DCs. Thus, through distinct mechanisms that are contingent upon the context, Tα1 represents a plausible candidate to improve the safety/efficacy profile of immune checkpoint inhibitors. ER -