Back to Search
Start Over
DUX4 is a common driver of immune evasion and immunotherapy failure in metastatic cancers.
- Source :
-
eLife . 6/3/2024, p1-26. 26p. - Publication Year :
- 2024
-
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 1 year. Our data motivate future attempts to develop DUX4 as a biomarker and therapeutic target for checkpoint immunotherapy resistance. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2050084X
- Database :
- Academic Search Index
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- 177786073
- Full Text :
- https://doi.org/10.7554/eLife.89017