{"doi":"10.1038/s41591-020-01212-6","title":"Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma","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.","journal":"Nature Medicine","year":2021,"id":12668,"datarank":0.7037021823343717,"base_score":4.6913478822291435,"endowment":4.6913478822291435,"self_citation_contribution":0.7037021823343717,"citation_network_contribution":0.0,"self_endowment_contribution":0.7037021823343717,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":108,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0523,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-25","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":28985,"name":"Cyril Neftel","orcid":"0000-0002-6356-1142","position":1,"is_corresponding":false},{"id":5553,"name":"Marni E. 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