ArticleNature medicine2021
Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma.
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Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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90citing papers in PubMed
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Who cites it
90 citing papers in PubMed, 117 citations in OpenAlex.
- Pleomorphism in Soft Tissue Sarcomas: Molecular Characteristics and Clinical Features.Medical sciences (Basel, Switzerland) · 2026Review
- Advances in single-cell and spatial multi-omics for plant development and stress responses.Plant diversity · 2026Review
- Fusion-driven oncogenic programs shape the immune landscape in translocation renal cell carcinoma.Nature communications · 2026Article
- Preliminary study on the mechanism of OPN up-regulating PD-L1 to induce CD8 + T cell exhaustion in synovial sarcoma.BMC cancer · 2026Article
- LPAR4 mediates resistance to interferon-induced stress in soft tissue sarcoma.Science advances · 2026Article
- Pan-cancer single-cell and spatial transcriptomics analyses delineate response-associated heterogeneity and therapeutic targets of tumor-infiltrating B cells following immune checkpoint blockade.Cancer immunology, immunotherapy : CII · 2026Article
- ScSpTITH: a rank-correlation framework for robust quantification of multi-dimensional tumor heterogeneity.Human genetics · 2026Article
- Review
- Revealing novel subtypes of synovial sarcoma through single cell transcriptomics.NPJ systems biology and applications · 2026Article
- Epigenetic remodeling in sarcoma promotes T-cell infiltration via modulation of the Hippo pathway.Journal for immunotherapy of cancer · 2026Article
- Single-Cell RNA Analysis of Murine Osteosarcoma Uncovers Skp2 Function in Metastasis, Genomic Instability, and Immune Activation and Reveals Additional Target Pathways.Cancer research communications · 2026Article
- High-content CRISPR activation screens identify synthetically lethal RNA-based mechanisms to sensitize cancer cells to targeted T cell cytotoxicity.Nature genetics · 2026Article
- Machine Learning-Based Transcriptomic Diagnosis of Periodontitis.International dental journal · 2026Article
- IL-9 as a naturally orthogonal cytokine with optimal JAK/STAT signaling for engineered T cell therapy.Immunity · 2026Article
- Primary pulmonary artery synovial sarcoma: a case report.AME case reports · 2026Article
- Tissue-Based Multiomic Exploratory Analysis of the Urokinase Plasminogen Activator/uPAR System and Matrix Metalloproteinases in Stroma AReactive Invasion Front Areas-Positive Gastrointestinal Cancers.Pathobiology : journal of immunopathology, molecular and cellular biology · 2026Article
- Primary Cardiac Synovial Sarcoma (PCSS): Clinicopathologic Features of 6 Cases and Literature Comparison.Cardiology research and practice · 2026Article
- Cancer-associated fibroblast subtype signature gene predicts survival and immunotherapy response in sarcoma.PloS one · 2026Article
- Synovial sarcoma reprograms transcription by GBAF activation of polycomb targets and loss of CBAF enhancers.Nature communications · 2025Article
- Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
50 authors at 8 institutions in 2 countries.
Livnat Jerby-Arnon *Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-4037-386X
Cyril Neftel *Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Marni E ShoreBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Hannah R WeismanBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Nathan D MathewsonDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8895-2609
Matthew J McBrideDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Brian HaasBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Benjamin IzarBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2379-6702
Angela VolorioBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Gaylor BoulayBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Luisa CironiInstitute of Pathology, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Alyssa R RichmanBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Liliane C BroyeInstitute of Pathology, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Joseph M GurskiMassachusetts General Hospital Cancer Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1668-3542
Christina C LuoDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Ravindra MylvaganamDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Lan NguyenBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Shaolin MeiLaboratory for Systems Pharmacology, Harvard Medical School, Boston, MA, USA.
Johannes C MelmsColumbia Center for Translational Immunology, New York, NY, USA.
Christophe GeorgescuBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Ofir CohenBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Jorge E Buendia-BuendiaDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Asa SegerstolpeBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Malika SudBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Michael S CuocoBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2163-5120
Danny LabesFlow Cytometry Facility, Department of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Simon GritschBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Daniel R ZollingerNanoString Technologies, Seattle, WA, USA.
Nicole OrtogeroNanoString Technologies, Seattle, WA, USA.
Joseph M BeechemNanoString Technologies, Seattle, WA, USA.
G Petur NielsenDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Ivan ChebibMassachusetts General Hospital Cancer Center, Boston, MA, USA.
Tu Nguyen-NgocDepartment of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Michael MontemurroDepartment of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Gregory M CoteDepartment of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA.
Edwin ChoyDepartment of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9896-8084
Igor LetovanecInstitute of Pathology, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Stéphane CherixDepartment of Orthopedics, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.ORCID http://orcid.org/0000-0001-5500-0508
Nikhil WagleBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Peter K SorgerLaboratory for Systems Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3364-1838
Alex B HaynesDepartment of Surgery, Massachusetts General Hospital, Boston, MA, USA.
John T MullenDepartment of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Ivan StamenkovicInstitute of Pathology, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Miguel N RiveraBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Cigall KadochBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4058-5985
Kai W WucherpfennigBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Orit Rozenblatt-RosenBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6313-3570
Mario L SuvàBroad Institute of Harvard and MIT, Cambridge, MA, USA. Suva.Mario@mgh.harvard.edu.ORCID http://orcid.org/0000-0001-9898-5351
Nicolò RiggiDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. nicolo.riggi@chuv.ch.ORCID http://orcid.org/0000-0001-9160-1984
Aviv RegevBroad Institute of Harvard and MIT, Cambridge, MA, USA. aregev@broadinstitute.org.ORCID http://orcid.org/0000-0003-3293-3158
Broad Institute · USUniversity Hospital of Lausanne · CHHarvard University · USMassachusetts General Hospital · USNanostring Technologies (United States) · USBrigham and Women's Hospital · USColumbia University Irving Medical Center · USUniversity of Lausanne · CH
Funding
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Andreea O'Connell · 1985 to 2026
$93.9MSystems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SHARPE, ARLENE H. · 2018 to 2022
$10.8MTrinity: Transcriptome assembly for genetic and functional analysis of cancerU24CA180922 · NCI · BROAD INSTITUTE, INC. · PI HAAS, BRIAN · 2013 to 2022
$7.5MDissecting the cellular hierarchies of malignant gliomas by single-cell functional genomicsR37CA245523 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Mario Luca Suva · 2020 to 2026
$2.8MOpen Software and Resource Development Leveraging Next-gen Sequencing Data to Facilitate Computational Analysis of Cancer BiologyR50CA211461 · NCI · BROAD INSTITUTE, INC. · PI HAAS, BRIAN · 2016 to 2020
$1.7MClinical implementation of single cell tumor transcriptome analysisR33CA202820 · NCI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R., JOHNSON, BRUCE E. · 2016 to 2018
$1.3MDissecting mechanisms of immunotherapy resistance in melanoma patientsK08CA222663 · NCI · DANA-FARBER CANCER INST · PI IZAR, BENJAMIN · 2017 to 2021
$827kBroad Institute R37CA245523Burroughs Wellcome Fund (BWF) 1019508Burroughs Wellcome Fund (BWF) K08CA222663Harvard Medical School CA225088NCI NIH HHS K08 CA222663NCI NIH HHS L30 CA231679NCI NIH HHS P30 CA014051NCI NIH HHS R33 CA202820NCI NIH HHS R37 CA245523NCI NIH HHS R50 CA211461NCI NIH HHS U24 CA180922NCI NIH HHS U54 CA225088Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) PP00P3-157468/1Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) PP00P3_183724
Abstract
Synovial sarcoma (SyS) is an aggressive neoplasm driven by the SS18-SSX fusion, and is characterized by low T cell infiltration. Here, we studied the cancer-immune interplay in SyS using an integrative approach that combines single-cell RNA sequencing (scRNA-seq), spatial profiling and genetic and pharmacological perturbations. scRNA-seq of 16,872 cells from 12 human SyS tumors uncovered a malignant subpopulation that marks immune-deprived niches in situ and is predictive of poor clinical outcomes in two independent cohorts. Functional analyses revealed that this malignant cell state is controlled by the SS18-SSX fusion, is repressed by cytokines secreted by macrophages and T cells, and can be synergistically targeted with a combination of HDAC and CDK4/CDK6 inhibitors. This drug combination enhanced malignant-cell immunogenicity in SyS models, leading to induced T cell reactivity and T cell-mediated killing. Our study provides a blueprint for investigating heterogeneity in fusion-driven malignancies and demonstrates an interplay between immune evasion and oncogenic processes that can be co-targeted in SyS and potentially in other malignancies.
Indexed as
Molecular Targeted TherapyCarcinogenesisCell Line, TumorCyclin-Dependent Kinase 4Histone Deacetylase InhibitorsHistone DeacetylasesHumansOncogene Proteins, FusionOncogenesRNA-SeqSarcoma, SynovialSingle-Cell AnalysisCyclin-Dependent Kinase 4Histone Deacetylase InhibitorsHistone DeacetylasesOncogene Proteins, Fusion
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