DNA Repair Gene Mutations as Predictors of Immune Checkpoint Inhibitor Response beyond Tumor Mutation Burden
Year: 2020
Type: article
Study design: Observational Study
Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but prediction of their benefit is challenging. Neoantigens generated through impaired non-mismatch DNA repair may result in greater ICI activity. By analyzing 1,661 ICI-treated patients, we show that deletions and mutations in nucleotide excision repair (NER) and homologous repair (HR) pathways are predictors of ICI benefit independent of tumor mutation burden and tumor type. NER and HR mutations are also associated with objective response rates to ICIs in esophagogastric and non-small-cell lung cancers. In a cohort of 40,181 unique patients, NER and HR mutations are present in 3.4% and 13.9% of cancers, respectively. These results indicate that NER and HR gene mutations occur in a subpopulation of cancer patients and may aid patient selection for ICI therapy. Assessing NER and HR mutations in the context of other biomarkers may yield powerful predictors of ICI activity across different cancer types.
Source: Cell Reports Medicine
Authors: David Hsiehchen, Antony Hsieh, Robert M. Samstein, Tianshi Lu, Muhammad S. Beg, David E. Gerber, Tao Wang, Luc G.T. Morris, Hao Zhu
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: American Association for Cancer Research, AstraZeneca, Cancer Prevention and Research Institute of Texas, Alnylam Pharmaceuticals, National Institutes of Health, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Dental and Craniofacial Research
Awards: Identifying and targeting neoantigens in aggressive salivary carcinomas, Dissecting cellular heterogeneity of bulk tumors for prediction of overall survival and responsive patients to immunotherapy, Reactivation of embryonic growth programs in liver cancer, Enhancing mammalian liver repair and regeneration, G5570506212, Development of New Cancer Treatments and Investigators, G9000053102, Cancer Center Support Grant, North American Star Consortium, The Johns Hopkins Translational Science Team and Consortium for ETCTN Studies, UT Southwestern Medical Center Simmons Comprehensive Cancer Center
OpenAlex ID: W3037527105