Abstract
ABSTRACTCancer 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 thatDUX4expression is a common feature of metastatic tumors, with ∼10-50% of advanced bladder, breast, kidney, prostate, and skin cancers expressingDUX4.DUX4expression is significantly associated with immune cell exclusion and decreased objective response to PD-L1 blockade in a large cohort of urothelial carcinoma patients.DUX4expression is a significant predictor of survival even after accounting for tumor mutational burden and other molecular and clinical features in this cohort, withDUX4expression 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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1. Pioneer factors in viral infection;Frontiers in Immunology;2023-10-09