Moving towards personalized treatments of immune-related adverse events
- 31 July 2020
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Clinical Oncology
- Vol. 17 (8), 504-515
- https://doi.org/10.1038/s41571-020-0352-8
Abstract
The treatment of immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors has mostly been based on adapting therapeutic approaches used in the management of primary autoimmune diseases. The authors of this Review provide an overview of the different cellular and soluble immune factors involved in the pathogenesis of irAEs in order to help clinicians deliver personalized immunopathologically guided treatment to manage these adverse events. The enhancement of immune responses upon treatment with immune checkpoint inhibitors can have the desired outcome of reinvigorating antitumour immune surveillance, but often at the expense of immune-related adverse events (irAEs). This novel disease entity often prompts comparisons with, and extrapolation of treatment approaches from, primary autoimmune disorders. Accordingly, current treatment guidelines for irAEs make generic recommendations adapted from the literature describing primary autoimmune diseases, without taking into consideration the substantial disparity of the immunohistopathological findings within each organ affected by an irAE. The treatment modalities themselves are complex and have many potential drawbacks, such as serious and rarely fatal infections, drug toxicities overlapping with irAEs and the risk of compromising cancer immune surveillance. Herein, we provide an overview of key cellular and soluble immunological factors mediating irAEs and propose a model integrating this knowledge with the immunohistopathological findings of the affected organs for a personalized decision-making process for each patient.This publication has 179 references indexed in Scilit:
- Treating inflammation by blocking interleukin-1 in a broad spectrum of diseasesNature Reviews Drug Discovery, 2012
- Incidence and management of mTOR inhibitor-associated pneumonitis in patients with metastatic renal cell carcinomaAnnals of Oncology, 2012
- Regulation of Immune Responses by mTORAnnual Review of Immunology, 2012
- Improved Survival with Ipilimumab in Patients with Metastatic MelanomaThe New England Journal of Medicine, 2010
- Autoinflammatory Disease Reloaded: A Clinical PerspectiveCell, 2010
- Circulating CD21lowB cells in common variable immunodeficiency resemble tissue homing, innate-like B cellsProceedings of the National Academy of Sciences of the United States of America, 2009
- An Autoinflammatory Disease Due to Homozygous Deletion of theIL1RNLocusThe New England Journal of Medicine, 2009
- IL-6 and Stat3 Are Required for Survival of Intestinal Epithelial Cells and Development of Colitis-Associated CancerCancer Cell, 2009
- A Proposed Classification of the Immunological DiseasesPLoS Medicine, 2006
- Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cellsNature, 2006