Affiliation:
1. Division of Population Sciences Dana‐Farber Cancer Institute and Harvard Medical School Boston Massachusetts USA
2. Division of Genetics Brigham & Women's Hospital Boston Massachusetts USA
3. The Broad Institute Cambridge Massachusetts USA
Abstract
SummaryCancer immunotherapy has revolutionized the treatment of advanced cancers and is quickly becoming an option for early‐stage disease. By reactivating the host immune system, immunotherapy harnesses patients' innate defenses to eradicate the tumor. By putatively similar mechanisms, immunotherapy can also substantially increase the risk of toxicities or immune‐related adverse events (irAEs). Severe irAEs can lead to hospitalization, treatment discontinuation, lifelong immune complications, or even death. Many irAEs present with similar symptoms to heritable autoimmune diseases, suggesting that germline genetics may contribute to their onset. Recently, genome‐wide association studies (GWAS) of irAEs have identified common germline associations and putative mechanisms, lending support to this hypothesis. A wide range of well‐established GWAS methods can potentially be harnessed to understand the etiology of irAEs specifically and immunotherapy outcomes broadly. This review summarizes current findings regarding germline effects on immunotherapy outcomes and discusses opportunities and challenges for leveraging germline genetics to understand, predict, and treat irAEs.
Funder
National Institutes of Health
Subject
Immunology,Immunology and Allergy
Cited by
2 articles.
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