Immune related adverse events (irAEs) have been observed with all checkpoint inhibitors and are very frequent. The evidences coming from experimental models of congenital or acquired deficiency of CTLA-4 or from PD-1 knock-out mice, provided all the informations to interpret the organ or systemic manifestations (endocrine, or systemic autoimmune chronic inflammatory diseases-ACIDs) observed in trials as well as in registries of cohorts treated with anti-CTLA-4 or anti-PD-1/PD-L1 inhibitors, or combination therapies. Finally the concern raised by cancers occurring in patients with autoimmune diseases (Systemic Lupus Erythematosus, Myositis, Rheumatoid Arthritis, Psoriatic Arthritis, Vasculitis, Scleroderma, Polymyalgia Rheumatica and others) and how to deal with immunotherapy was discussed. The biological knowledges acquired with the immunotherapy trials, have paved to way to better treat autoimmune diseases in patients developing cancer during the autoimmune illness. Immunotherapy without Autoimmunity is the unmet need within our reach in the future.Copyright © 2019. Published by Elsevier Inc.