{
  "abstract": "Background Response to immune checkpoint inhibition (ICI) in sarcomas is overall low and heterogeneous. Understanding determinants of ICI outcomes may improve efficacy and patient selection. Thus, we investigated whether the expression of transposable elements (TEs), which are epigenetically silenced and can stimulate antitumor immunity, influence ICI outcomes and immune infiltrates in common sarcoma subtypes.Methods We used transcriptomic data to assign immune enhanced versus immune depleted status to 67 pretreatment and on-treatment biopsies of sarcomas from patients treated on ICI trials, along with additional cohorts from The Cancer Genome Atlas (TCGA) and an independent ICI trial (SARC028). A machine learning technique (lasso-penalized logistic regression) controlled for sarcoma subtype was used to determine if TE and epigenetic regulatory gene expression predict immune infiltrates. Correlations between top features in these models and sarcoma immune infiltrates, immune pathway expression, and clinical outcomes were explored.Results Expression of TEs and epigenetic regulators significantly predicted immune enhanced status. TE subfamilies and Ikaros family zinc finger 1 ( IKZF1), a chromatin-modulating transcription factor, were significantly contributory. TE and IKZF1 expression positively correlated with tumor immune infiltrates, inflammatory pathways, and improved clinical outcomes, and increased in tumors that gained immune infiltrates during ICI treatment. TE and IKZF1 expression similarly correlated with overall survival and immune features in a TCGA cohort. In an additional cohort of patients with sarcoma treated with ICI, IKZF1 expression correlated with progression-free survival and inflammatory features.Conclusions TE and IKZF1 expression warrant further translational investigation as potential biomarkers of tumor immune infiltrates and outcomes following ICI treatment, and as therapeutic targets in sarcomas.",
  "authors": [
    {
      "affiliations": [
        "Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA",
        "UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Benjamin A Nacev"
    },
    {
      "affiliations": [
        "Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Martina Bradic"
    },
    {
      "affiliations": [
        "Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Hyung Jun Woo"
    },
    {
      "affiliations": [
        "Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Allison L Richards"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Ciara M Kelly"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Mark A Dickson"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Mrinal M Gounder"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Mary L Keohan"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Ping Chi"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Sujana Movva"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Robert G Maki"
    },
    {
      "affiliations": [
        "Weill Cornell Medical College, New York, New York, USA",
        "Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA"
      ],
      "name": "Emily K Slotkin"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Evan Rosenbaum"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Viswatej Avutu"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Jason E Chan"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Lauren B Banks"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Travis Adamson"
    },
    {
      "affiliations": [
        "Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Samuel Singer"
    },
    {
      "affiliations": [
        "Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Cristina R Antonescu"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "William D Tap"
    },
    {
      "affiliations": [
        "Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Mark TA Donoghue"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Sandra P D’Angelo"
    }
  ],
  "title": "High transposable element expression in sarcomas is associated with increased immune infiltrates and improved outcomes including after immunotherapy",
  "uid": "55795214-1fe0-586a-8cfb-7e158da71327"
}