Proliferative CD8 T-cells : A Novel Immune Microenvironmental Determinant of Outcomes in Multiple Myeloma

Proliferative CD8 T-cells : A Novel Immune Microenvironmental Determinant of Outcomes in Multiple Myeloma | 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 Article Proliferative CD8 T-cells : A Novel Immune Microenvironmental Determinant of Outcomes in Multiple Myeloma Sanjay de Mel, Jonathan Scolnick, Chern Han Yong, Stacy Xu, Xiaojing Huo, and 17 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6929982/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 Multiple myeloma (MM) remains incurable despite major therapeutic advances, and the tumor microenvironment (TME) plays an important role in disease progression. Since T-cell dysfunction is of particular importance in MM, we hypothesised that dysfunctional cytotoxic T cells may be associated with adverse outcomes. We conducted single-cell multi-omic sequencing of newly-diagnosed MM to identify TME determinants of progression free survival (PFS). In a discovery cohort, we identified a cluster of proliferative CD8+ cells whose proportion in the bone marrow was associated with inferior PFS, independent of clinical covariates. This association was validated in an independent validation cohort, as well as in a tissue microarray cohort using multiplexed immunofluorescence. These proliferative CD8+ cells showed inconsistent expression of T-cell exhaustion genes and had a gene expression profile overlapping with a similar population described in solid tumors. Our results show that proliferative CD8+ cells are an important mediator of adverse outcomes in MM, and motivate further investigation into the ontogeny and functional characteristics of this population. Health sciences/Oncology Health sciences/Oncology/Cancer Health sciences/Oncology/Cancer/Haematological cancer Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryTables.xlsx Supplementary tables CombinedSupplementaryMethodsandFigures.pdf Combined Supplementary Methods and Figures 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. 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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-6929982","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":479143711,"identity":"fb01d785-ef81-40d3-92b7-4e9c4fab8b31","order_by":0,"name":"Sanjay de Mel","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-8881-3537","institution":"National University Cancer Institute Singapore National University Health System Singapore","correspondingAuthor":true,"prefix":"","firstName":"Sanjay","middleName":"","lastName":"de Mel","suffix":""},{"id":479143712,"identity":"5243e8a4-fbc7-4f6f-9576-92829661ffc8","order_by":1,"name":"Jonathan Scolnick","email":"","orcid":"","institution":"Singleron Biotechnologies Pte Ltd, Singapore","correspondingAuthor":false,"prefix":"","firstName":"Jonathan","middleName":"","lastName":"Scolnick","suffix":""},{"id":479143713,"identity":"19a22feb-d0f3-46f9-ac2b-60ffda7e178c","order_by":2,"name":"Chern Han Yong","email":"","orcid":"https://orcid.org/0000-0001-5176-4543","institution":"National University of Singapore","correspondingAuthor":false,"prefix":"","firstName":"Chern","middleName":"Han","lastName":"Yong","suffix":""},{"id":479143714,"identity":"15267cda-8f7f-430d-a9b3-3fd5a3e8a094","order_by":3,"name":"Stacy Xu","email":"","orcid":"","institution":"Singleron Biotechnologies Pte Ltd, Singapore","correspondingAuthor":false,"prefix":"","firstName":"Stacy","middleName":"","lastName":"Xu","suffix":""},{"id":479143715,"identity":"a666b3d0-4c9a-4741-8a8d-f44e7ddbf657","order_by":4,"name":"Xiaojing Huo","email":"","orcid":"","institution":"Singleron Biotechnologies Pte Ltd, Singapore","correspondingAuthor":false,"prefix":"","firstName":"Xiaojing","middleName":"","lastName":"Huo","suffix":""},{"id":479143716,"identity":"42778aaf-a242-451d-8f95-325fa708f8e3","order_by":5,"name":"Cinnie Soekojo","email":"","orcid":"","institution":"National University Cancer Institute Singapore. 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