Opposing immune and genetic forces shape oncogenic programs in synovial sarcoma
Marni E. Shore,
Matthew J. McBride,
Hannah R. Weissman,
Alyssa R. Richman,
Liliane C. Broye,
Joseph M. Gurski,
Christina C. Luo,
Johannes c. Melms,
Jorge E Buendia-Buendia,
Michael S Cuoco,
Daniel R. Zollinger,
Joseph M. Beechem,
G. Petur Nielsen,
Peter K. Sorger,
Alex B. Haynes,
John T. Mullen,
Miguel N. Rivera,
Mario L. Suvà,
Posted 04 Aug 2019
bioRxiv DOI: 10.1101/724302
Posted 04 Aug 2019
Synovial sarcoma is an aggressive mesenchymal neoplasm, driven by the SS18-SSX fusion, and characterized by immunogenic antigens expression and exceptionally low T cell infiltration levels. To study the cancer-immune interplay in this disease, we profiled 16,872 cells from 12 human synovial sarcoma tumors using single-cell RNA-sequencing (scRNA-Seq). Synovial sarcoma manifests antitumor immunity, high cellular plasticity and a core oncogenic program, which is predictive of low immune levels and poor clinical outcomes. Using genetic and pharmacological perturbations, we demonstrate that the program is controlled by the SS18-SSX driver and repressed by cytokines secreted by macrophages and T cells in the tumor microenvironment. Network modeling predicted that SS18-SSX promotes the program through HDAC1 and CDK6. Indeed, the combination of HDAC and CDK4/6 inhibitors represses the program, induces immunogenic cell states, and selectively targets synovial sarcoma cells. Our study demonstrates that immune evasion, cellular plasticity, and cell cycle are co-regulated and can be co-targeted in synovial sarcoma and potentially in other malignancies.
- Downloaded 1,265 times
- Download rankings, all-time:
- Site-wide: 12,019 out of 118,417
- In cancer biology: 263 out of 3,748
- Year to date:
- Site-wide: 10,336 out of 118,417
- Since beginning of last month:
- Site-wide: 16,615 out of 118,417
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!