SPP1+ macrophages in HR+ breast cancer are associated with tumour-infiltrating lymphocytes

SPP1+ macrophages in HR+ breast cancer are associated with tumour-infiltrating lymphocytes | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Article SPP1+ macrophages in HR+ breast cancer are associated with tumour-infiltrating lymphocytes Hee Jin Lee, Su Min Cha, Jung-Wook Park, Yoon Jae Lee, Hee Jae Lee, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3874740/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Breast cancer, categorised into hormone receptor-positive (HR+), HER2- positive (HER2+), and triple-negative (TNBC) subtypes, exhibits varied outcomes based on the number of tumour-infiltrating lymphocytes (TILs). Increased TIL levels are associated with better outcomes in HER2+ and TNBC, while HR+ individuals with high TIL levels show shorter survival but greater neoadjuvant chemotherapy response. To explore the divergent roles of TIL levels across various subtypes and their effect on immune cell composition, we employed single-cell RNA sequencing on 31 patients with breast cancer. HR+ breast cancer with high TIL levels (TIL-high) revealed increased SPP1+ macrophages, increased SPP1 expression in other monocytes/macrophages (mono/macro) subgroups, and enriched pathways associated with extracellular matrix (ECM) remodelling in mono/macro. Moreover, cell–cell interaction analyses revealed enhanced SPP1, MIF, and FN1 signalling in the interaction between SPP1+ macrophages and T-cells in TIL-high HR+ breast cancer. Spatial transcriptomics data highlighted the close proximity of SPP1+ macrophages, CD8+ T-cells, and CD4+ T-cells in TIL-high HR+ breast cancer. Our findings unveil the novel influence of SPP1+ macrophages on T-cells in TIL-high HR+ breast cancer, potentially explaining the poor prognosis and offering insights for targeted interventions. Biological sciences/Cancer/Breast cancer Biological sciences/Cancer/Cancer microenvironment Biological sciences/Cancer/Tumour heterogeneity Breast cancer Hormone receptor (HR) Tumour-infiltrating lymphocytes Tumour-associated macrophages Secreted Phosphoprotein 1 Full Text Additional Declarations (Not answered) Supplementary Files 3.Supplementaryinformation.pdf Supplementaryfigure1.pdf Supplementaryfigure2.pdf Supplementaryfigure3.pdf Supplementaryfigure4.pdf Supplementaryfigure5.pdf Supplementaryfigure6.pdf Supplementaryfigure7.pdf Supplementaryfigure8.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: revise 11 Mar, 2024 Review # 3 received at journal 08 Mar, 2024 Review # 1 received at journal 06 Mar, 2024 Review # 2 received at journal 05 Mar, 2024 Reviewer # 3 agreed at journal 26 Feb, 2024 Reviewer # 2 agreed at journal 26 Feb, 2024 Reviewer # 1 agreed at journal 26 Feb, 2024 Reviewers invited by journal 25 Feb, 2024 Editor assigned by journal 19 Jan, 2024 Submission checks completed at journal 18 Jan, 2024 First submitted to journal 18 Jan, 2024 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. 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Also discoverable on Platform About In Review Editorial Policies 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-3874740","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":274871548,"identity":"02093ebd-9902-4f4b-8978-0b082fd36041","order_by":0,"name":"Hee Jin 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