Proteogenomic and single-cell dissection of immune heterogeneity in NSMP endometrial cancer reveals dual IDO1 programs

Proteogenomic and single-cell dissection of immune heterogeneity in NSMP endometrial cancer reveals dual IDO1 programs | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Proteogenomic and single-cell dissection of immune heterogeneity in NSMP endometrial cancer reveals dual IDO1 programs Osman Bilge Kaya, Berkan Karabuğa, Ergin Aydemir, Elif Sertesen Çamöz, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9688861/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The no-specific-molecular-profile (NSMP) subtype is the largest and most clinically heterogeneous group of endometrial cancers, but its immune microenvironment remains poorly characterised. Integrating transcriptomic (TCGA-UCEC; n = 145), genomic (MSK-IMPACT; n = 108), proteogenomic (CPTAC-UCEC; n = 43) and paired-sample single-cell (GSE251923; 17,539 cells) data, we show that NSMP harbours the widest immune heterogeneity of any molecular subtype, driven by impaired T-cell infiltration rather than antigen-presentation loss. Weighted gene co-expression network analysis identified a 121-gene macrophage/APC module (MEblack) that stratifies NSMP into Immune-High and Immune-Low phenotypes; the Immune-High subgroup shows selective MHC class II elevation and IDO1 upregulation, both validated at the protein level. At single-cell resolution, MEblack is macrophage-specific and IDO1 segregates into IFN-γ-coupled adaptive (myeloid) and IFN-γ-uncoupled constitutive (tumour-intrinsic) programs. A combined MEblack/IDO1 biomarker may identify pMMR patients suitable for IDO1-targeted immunotherapy. Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9688861","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":638975421,"identity":"016c89e2-2381-4362-9105-168ed087d043","order_by":0,"name":"Osman Bilge 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