IFI16-dependent STING signaling is a crucial regulator of anti-HER2 immune response in HER2+ breast cancer
Agency for Science, Technology and Research · University of Michigan · +12 more institutions
Abstract
Relapse to anti-HER2 monoclonal antibody (mAb) therapies, such as trastuzumab in HER2 + breast cancer (BC), is associated with residual disease progression due to resistance to therapy. Here, we identify interferon-γ inducible protein 16 (IFI16)-dependent STING signaling as a significant determinant of trastuzumab responses in HER2 + BC. We show that down-regulation of immune-regulated genes (IRG) is specifically associated with poor survival of HER2 + , but not other BC subtypes. Among IRG, IFI16 is identified as a direct target of EZH2, the underexpression of which leads to deficient STING activation and downstream CXCL10/11 expression in response to trastuzumab treatment. Dual inhibition of EZH2 and histone…
Citation impact
- FWCI
- 47.87
- Percentile
- 100%
- References
- 63
Authors
19- LOL.S. OngCorresponding
Agency for Science, Technology and Research, University of Michigan, Genome Institute of Singapore
- WCWee Chyan Lee
Agency for Science, Technology and Research, University of Michigan, Genome Institute of Singapore
- SMShijun Ma
Agency for Science, Technology and Research, University of Michigan, Genome Institute of Singapore
- GOGokce Oguz
Agency for Science, Technology and Research, University of Michigan, Genome Institute of Singapore
- ZNZhitong Niu
Sun Yat-sen University, Sixth Affiliated Hospital of Sun Yat-sen University
Topics & keywords
- Trastuzumab
- Cancer research
- EZH2
- Histone deacetylase
- Immune system
- Histone deacetylase inhibitor
- Breast cancer
- Signal transduction
- Good health and well-being