@article{2ed9dc3aae0a454d87bec74c1db493a0,
title = "Pharmacological disruption of the MTDH–SND1 complex enhances tumor antigen presentation and synergizes with anti-PD-1 therapy in metastatic breast cancer",
abstract = "Despite increased overall survival rates, curative options for metastatic breast cancer remain limited. We have previously shown that metadherin (MTDH) is frequently overexpressed in poor prognosis breast cancer, where it promotes metastasis and therapy resistance through its interaction with staphylococcal nuclease domain-containing 1 (SND1). Through genetic and pharmacological targeting of the MTDH–SND1 interaction, we reveal a key role for this complex in suppressing antitumor T cell responses in breast cancer. The MTDH–SND1 complex reduces tumor antigen presentation and inhibits T cell infiltration and activation by binding to and destabilizing Tap1/2 messenger RNAs, which encode key components of the antigen-presentation machinery. Following small-molecule compound C26-A6 treatment to disrupt the MTDH–SND1 complex, we showed enhanced immune surveillance and sensitivity to anti-programmed cell death protein 1 therapy in preclinical models of metastatic breast cancer, in support of this combination therapy as a viable approach to increase immune-checkpoint blockade therapy responses in metastatic breast cancer.",
author = "Minhong Shen and Smith, {Heath A.} and Yong Wei and Jiang, {Yi Zhou} and Sheng Zhao and Nicole Wang and Michelle Rowicki and Yong Tang and Xiang Hang and Songyang Wu and Liling Wan and Shao, {Zhi Ming} and Yibin Kang",
note = "Funding Information: We thank G. Ren, W. Li, Z. Li, W. Lu and other laboratory members for technical support and helpful discussions. We thank W. Wang at the Genomics Core Facility of Princeton University for RNA-seq, C. DeCoste and K. Rittenbach at the Molecular Biology Flow Cytometry Resource Facility of Princeton University for the flow cytometry assays. We thank W. Zhang (University of Florida) for providing the E0771 cells. This research was supported by the Brewster Foundation and Ludwig Cancer Research and grants from the Breast Cancer Research Foundation, the National Institutes of Health (no. R01CA134519), Department of Defense Breast Cancer Research Program (no. BC151403), American Cancer Society and Susan G. Komen Foundation to Y.K. and postdoctoral fellowships from Susan G. Komen (no. PDF17332118) and NJCCR (no. DFHS15PPCO21) to M.S. This research was also supported by the Preclinical Imaging and Flow Cytometry Shared Resources of the Rutgers Cancer Institute of New Jersey (no. P30CA072720). Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = jan,
doi = "10.1038/s43018-021-00280-y",
language = "English (US)",
volume = "3",
pages = "60--74",
journal = "Nature Cancer",
issn = "2662-1347",
publisher = "Nature Research",
number = "1",
}