title: Opportunistic Autoimmune Disorders Potentiated by Immune-Checkpoint Inhibitors Anti-CTLA-4 and Anti-PD-1.
abstract: To improve the efficacy of immunotherapy for cancer and autoimmune diseases, recent ongoing and completed clinical trials have focused on specific targets to redirect the immune network toward eradicating a variety of tumors and ameliorating the self-destructive process. In a previous review, both systemic immunomodulators and monoclonal antibodies (mAbs), anti-CTLA-4, and anti-CD52, were discussed regarding therapeutics and autoimmune sequelae, as well as predisposing factors known to exacerbate immune-related adverse events (irAEs). This review will focus on immune-checkpoint inhibitors, and the data from most clinical trials involve blockade with anti-CTLA-4 such as ipilimumab. However, despite the mild to severe irAEs observed with ipilimumab in ~60% of patients, overall survival (OS) averaged ~22-25% at 3-5 years. To boost OS, other mAbs targeting programed death-1 and its ligand are undergoing clinical trials as monotherapy or dual therapy with anti-CTLA-4. Therapeutic combinations may generate different spectrum of opportunistic autoimmune disorders. To simulate clinical scenarios, we have applied regulatory T cell perturbation to murine models combined to examine the balance between thyroid autoimmunity and tumor-specific immunity.
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Yi-Chi M
authors.initials: YC
authors.lastname: Kong
authors.affiliation: Department of Orthopaedic Surgery, Providence Hospital and Medical Centers , Southfield, MI , USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Flynn
keywords: anti-CTLA-4; anti-PD-1; autoimmune disease; immune-checkpoint inhibitor; tumor immunity