CD301b lectin expression in the breast tumor microenvironment augments tumor growth

CD301b lectin expression in the breast tumor microenvironment augments tumor growth | 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 CD301b lectin expression in the breast tumor microenvironment augments tumor growth Ahmet Ozdilek, Amy V. Paschall, Zahra Nawaz, Afaq M. M. Niyas, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8148605/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 Aberrant tumor glycosylation can alter immune recognition; however, the specific influence of glycan-lectin interactions on tumor progression remains poorly understood. Here, we identify the C-type lectin receptor CD301b (encoded by Mgl2 ) as a regulator of immune activity within the breast tumor microenvironment (TME). Using a murine triple-negative breast cancer model, we demonstrate that tumors expressing the Tn glycoantigen grow more rapidly, and this growth is facilitated by CD301b⁺ immune cells. Depletion or genetic loss of CD301b markedly suppressed tumor growth, indicating that CD301b promotes tumor progression through myeloid-tumor interactions. Phenotypic analyses revealed that CD301b⁺ cells within tumors are type 2 conventional dendritic cells (cDC2s), a subset known to influence immune polarization. Single-cell RNA sequencing of human breast cancers showed that the human ortholog CLEC10A is expressed in cDC2-like dendritic cells and select macrophage subsets, suggesting a conserved role for CD301⁺ myeloid populations. Transcriptomic profiling of tumors developed in Mgl2 -deficient mice revealed a shift toward an inflammatory, immune-activated state consistent with enhanced antitumor immunity. Together, these findings establish a link between tumor glycosylation and lectin signaling of myeloid cells, highlighting CD301b as a potential target for reprogramming the tumor immune microenvironment in breast cancer. Biological sciences/Cancer Biological sciences/Computational biology and bioinformatics Biological sciences/Immunology Health sciences/Oncology 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-8148605","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":554050584,"identity":"c5c5c0c9-6d7f-40d9-a133-de2f412939a8","order_by":0,"name":"Ahmet Ozdilek","email":"","orcid":"","institution":"Emory University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ahmet","middleName":"","lastName":"Ozdilek","suffix":""},{"id":554050585,"identity":"faf5674e-71e1-4d17-8f0f-9e0f0ca41aa8","order_by":1,"name":"Amy V. 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growth","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8148605/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8148605/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAberrant tumor glycosylation can alter immune recognition; however, the specific influence of glycan-lectin interactions on tumor progression remains poorly understood. Here, we identify the C-type lectin receptor CD301b (encoded by \u003cem\u003eMgl2\u003c/em\u003e) as a regulator of immune activity within the breast tumor microenvironment (TME). Using a murine triple-negative breast cancer model, we demonstrate that tumors expressing the Tn glycoantigen grow more rapidly, and this growth is facilitated by CD301b⁺ immune cells. Depletion or genetic loss of CD301b markedly suppressed tumor growth, indicating that CD301b promotes tumor progression through myeloid-tumor interactions. Phenotypic analyses revealed that CD301b⁺ cells within tumors are type 2 conventional dendritic cells (cDC2s), a subset known to influence immune polarization. Single-cell RNA sequencing of human breast cancers showed that the human ortholog CLEC10A is expressed in cDC2-like dendritic cells and select macrophage subsets, suggesting a conserved role for CD301⁺ myeloid populations. Transcriptomic profiling of tumors developed in \u003cem\u003eMgl2\u003c/em\u003e-deficient mice revealed a shift toward an inflammatory, immune-activated state consistent with enhanced antitumor immunity. Together, these findings establish a link between tumor glycosylation and lectin signaling of myeloid cells, highlighting CD301b as a potential target for reprogramming the tumor immune microenvironment in breast cancer.\u003c/p\u003e","manuscriptTitle":"CD301b lectin expression in the breast tumor microenvironment augments tumor growth","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-03 08:09:02","doi":"10.21203/rs.3.rs-8148605/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1bf43d9d-8c1a-43a0-975e-b63ae5bef0c5","owner":[],"postedDate":"December 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":58957228,"name":"Biological sciences/Cancer"},{"id":58957229,"name":"Biological sciences/Computational biology and bioinformatics"},{"id":58957230,"name":"Biological sciences/Immunology"},{"id":58957231,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-01-13T01:08:38+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-03 08:09:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8148605","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8148605","identity":"rs-8148605","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}