Year: 2023
Type: article
Study design: Observational Study
Abstract: ABSTRACT Cancer immune evasion contributes to checkpoint immunotherapy failure in many patients with metastatic cancers. The embryonic transcription factor DUX4 was recently characterized as a suppressor of interferon-γ signaling and antigen presentation that is aberrantly expressed in a small subset of primary tumors. Here, we report that DUX4 expression is a common feature of metastatic tumors, with ∼10-50% of advanced bladder, breast, kidney, prostate, and skin cancers expressing DUX4 . DUX4 expression is significantly associated with immune cell exclusion and decreased objective response to PD-L1 blockade in a large cohort of urothelial carcinoma patients. DUX4 expression is a significant predictor of survival even after accounting for tumor mutational burden and other molecular and clinical features in this cohort, with DUX4 expression associated with a median reduction in survival of over one year. Our data motivate future attempts to develop DUX4 as a biomarker and therapeutic target for checkpoint immunotherapy resistance.
Source: eLife
DOI: 10.7554/elife.89017
Institutions: University of Washington, Fred Hutch Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: University of Washington Medical Scientist Training Program, Interrogating the minor spliceosome to understand and treat leukemia, G887357334, G8956203657, University of Washington Medical Scientist Training Program, Genetic and molecular basis for SRSF2 mutations in myelodysplasia, Functional and molecular consequences of SF3B1 mutations in human hematopoietic stem cells
OpenAlex ID: W4386368825