Immune checkpoint inhibitors and irAEs

COPyRIGHT Copyright © 2018 by author(s) and EnPress Publisher LLC. This work is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). http://creativecommons.org/licenses/ by/4.0/ In the development of medicine, there are not many cases that advanced in a direction different from the original purpose. Sometimes it is practical in areas that no one expected. The immune checkpoints programmed cell death 1 (PD-1) is exactly that example. Dr. Hiroyuki Nishimura showed the development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Because of the wide range of ligand distribution in the body, its biological significance pervades almost every aspect of immune responses including autoimmunity, tumor immunity, infectious immunity, transplantation immunity, allergy and immunological privilege. Immune checkpoints inhibitors (ICIs) have opened promising avenues in the treatment of cancer. Various blocking antibodies targeting PD-1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are approved for human use. They significantly improved disease outcome in a number of cancer patients by boosting anti-tumor immune responses. As Seidel et al. described in their review article, mortality among advanced stage patients and the frequency of treatment-related adverse events remain high with current treatment.