Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy Journal Article
| Authors: | Subramanian, A.; Nemat-Gorgani, N.; Ellis-Caleo, T. J.; van Ijzendoorn, D. G. P.; Sears, T. J.; Somani, A.; Luca, B. A.; Zhou, M. Y.; Bradic, M.; Torres, I. A.; Oladipo, E.; New, C.; Kenney, D. E.; Avedian, R. S.; Steffner, R. J.; Binkley, M. S.; Mohler, D. G.; Tap, W. D.; D’Angelo, S. P.; van de Rijn, M.; Ganjoo, K. N.; Bui, N. Q.; Charville, G. W.; Newman, A. M.; Moding, E. J. |
| Article Title: | Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy |
| Abstract: | Characterization of the diverse malignant and stromal cell states that make up soft tissue sarcomas and their correlation with patient outcomes has proven difficult using fixed clinical specimens. Here, we employed EcoTyper, a machine-learning framework, to identify the fundamental cell states and cellular ecosystems that make up sarcomas on a large scale using bulk transcriptomes with clinical annotations. We identified and validated 23 sarcoma-specific, transcriptionally defined cell states, many of which were highly prognostic of patient outcomes across independent datasets. We discovered three conserved cellular communities or ecotypes associated with underlying genomic alterations and distinct clinical outcomes. We show that one ecotype defined by tumor-associated macrophages and epithelial-like malignant cells predicts response to immune-checkpoint inhibition but not chemotherapy and validate our findings in an independent cohort. Our results may enable identification of patients with soft tissue sarcomas who could benefit from immunotherapy and help develop new therapeutic strategies. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024. |
| Keywords: | genetics; sarcoma; gene expression regulation; gene expression regulation, neoplastic; immunology; immunotherapy; transcriptome; tumor microenvironment; tumor-associated macrophage; procedures; tumor-associated macrophages; machine learning; immune checkpoint inhibitor; humans; prognosis; human; immune checkpoint inhibitors |
| Journal Title: | Nature Cancer |
| Volume: | 5 |
| Issue: | 4 |
| ISSN: | 2662-1347 |
| Publisher: | Nature Research |
| Publication status: | Published |
| Date Published: | 2024-04-01 |
| Online Publication Date: | 2024-03-01 |
| Start Page: | 642 |
| End Page: | 658 |
| Language: | English |
| DOI: | 10.1038/s43018-024-00743-y |
| PUBMED: | 38429415 |
| PROVIDER: | scopus |
| PMCID: | PMC11058033 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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