biostudies-literatureNacev BAConnective Tissue Oncology SocietyIncyteWitherwax fundAmgenCycle for SurvivalBristol Myers SquibbNEKTARNational Cancer InstituteNCI NIH HHSHenry R. Kravis Center for Molecular OncologyDamon Runyon Cancer Research FoundationMercke012357https://www.ebi.ac.uk/biostudies/studies/S-EPMC12414182biostudies-literatureUnknown13(9)<h4>Background</h4>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.<h4>Methods</h4>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 fJournal for immunotherapy of cancerHigh transposable element expression in sarcomas is associated with increased immune infiltrates and improved outcomes including after immunotherapy.PMC12414182N/AP30 CA047904P30 CA008748K08CA245212K08 CA245212P30 CA08748CI-124-23Slotkin EKDickson MARichards ALAntonescu CRKeohan MLBanks LBKelly CMChan JETap WDAdamson TMovva SWoo HJAvutu VSinger SDonoghue MTNacev BAChi PBradic MRosenbaum EGounder MMMaki RGD'Angelo SPfalseHigh transposable element expression in sarcomas is associated with increased immune infiltrates and improved outcomes including after immunotherapy.<h4>Background</h4>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.<h4>Methods</h4>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 f2025-01-01T00:00:00Z2025 Sep2026-06-02T22:33:34.578Z2026-05-28T03:06:27.629ZS-EPMC124141824091274010.1136/jitc-2025-012357