Spatial Profiling Reveals Unique Immune Microenvironment in Premenopausal Triple-Negative Breast Cancer Associated with Therapy Response

Spatial Profiling Reveals Unique Immune Microenvironment in Premenopausal Triple-Negative Breast Cancer Associated with Therapy Response | 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 Spatial Profiling Reveals Unique Immune Microenvironment in Premenopausal Triple-Negative Breast Cancer Associated with Therapy Response Vidya P. Nimbalkar, V.P. Snijesh, Savitha Rajarajan, C.E. Anupama, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4811059/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Triple-negative breast cancer (TNBC) lacks targeted therapies, leading to poor prognosis. Younger TNBC patients exhibit distinct tumor microenvironments and aggressive disease. We explored the influence of menopausal status on immune landscapes, tumor progression, and therapy response using spatial profiling. Eleven treatment-naïve TNBC tumors were analyzed in epithelial and non-epithelial areas, revealing distinct clusters for premenopausal tumors with upregulated antigen presentation and cell activation pathways, and downregulated T cell checkpoint and PI3K-AKT pathways. External dataset validation (METABRIC, SCAN-B) associated these findings with better prognosis in premenopausal tumors. Immune profiling showed increased CD8 + T cells, monocytes, and endothelial cells, with higher intratumoral CD8, CD4, and CD20 protein expression. Therapy response analysis (I-SPY 2) indicated better responses to PARP and HSP90 inhibitors but reduced sensitivity to pembrolizumab and PI3K-AKT inhibitors in premenopausal tumors. These results highlight menopausal status as a critical factor in TNBC therapy and underscore the need for tailored treatment strategies. Oncology Triple Negative Breast Cancer Premenopausal Digital Spatial Profiling Tumor Microenvironment Immune Profiling Therapy response Full Text Additional Declarations The authors declare no competing interests. Supplementary Files supplementaryfile1.xlsx Supplementaryfile2.docx Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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-4811059","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":333520256,"identity":"b7800299-e1c3-4c4f-8a31-66ec5c425162","order_by":0,"name":"Vidya P. Nimbalkar","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Vidya","middleName":"P.","lastName":"Nimbalkar","suffix":""},{"id":333520257,"identity":"0f29e49f-6d45-4af5-8882-056c22c8146b","order_by":1,"name":"V.P. 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