Single-Cell and Spatial Transcriptomics Reveal a Tumor-Associated Macrophage Subpopulation that Mediates Prostate Cancer Progression and Metastasis

dc.contributor.authorMei, Shenglinen
dc.contributor.authorZhang, Hanyuen
dc.contributor.authorHirz, Taghreeden
dc.contributor.authorJeffries, Nathan Eliasen
dc.contributor.authorXu, Yanxinen
dc.contributor.authorBaryawno, Niniben
dc.contributor.authorWu, Shulinen
dc.contributor.authorWu, Chin-Leeen
dc.contributor.authorPatnaik, Akashen
dc.contributor.authorSaylor, Philip J.en
dc.contributor.authorSykes, David B.en
dc.contributor.authorDahl, Douglas M.en
dc.date.accessioned2025-07-15T19:15:00Zen
dc.date.available2025-07-15T19:15:00Zen
dc.date.issued2025-07-02en
dc.description.abstractTumor-associated macrophages (TAM) are a transcriptionally heterogeneous population, and their abundance and function in prostate cancer is poorly defined. We integrated parallel datasets from single-cell RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to reveal the dynamics of TAMs in primary and metastatic prostate cancer. Four TAM subpopulations were identified. Notably, one of these TAM subsets was defined by the co-expression of SPP1+ and TREM2+ and was significantly enriched in metastatic tumors. The SPP1+/TREM2+ TAMs were enriched in the metastatic tumor microenvironment in both human patient samples and murine models of prostate cancer. The abundance of these SPP1+/TREM2+ macrophages was associated with patient progression-free survival. Spatially, TAMs within prostate cancer bone metastases were highly enriched within the tumor region, consistent with their protumorigenic role. Blocking SPP1 in the RM1 prostate cancer mouse model led to improved efficacy of anti-PD-1 treatment and increased CD8+ T-cell infiltration in tumor. These findings suggest that targeting SPP1+ TAMs may offer a promising therapeutic strategy and potentially enhance the effects of immune checkpoint inhibition in advanced prostate cancer.<h4>Implications</h4>This study expands our understanding of the diverse roles of macrophage populations in prostate cancer metastases and highlights new therapeutic targets.en
dc.description.versionAccepted versionen
dc.format.extentPages 653-665en
dc.format.extent13 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1158/1541-7786.MCR-24-0791en
dc.identifier.eissn1557-3125en
dc.identifier.issn1541-7786en
dc.identifier.issue7en
dc.identifier.orcidMei, Shenglin [0000-0001-8258-5898]en
dc.identifier.other754251 (PII)en
dc.identifier.pmid40105746en
dc.identifier.urihttps://hdl.handle.net/10919/136480en
dc.identifier.volume23en
dc.language.isoenen
dc.publisherAmerican Association for Cancer Researchen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/40105746en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectProstate canceren
dc.subjectTumor-associated macrophagesen
dc.subjectMetastasisen
dc.subject.meshCell Line, Tumoren
dc.subject.meshAnimalsen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshProstatic Neoplasmsen
dc.subject.meshNeoplasm Metastasisen
dc.subject.meshDisease Progressionen
dc.subject.meshMaleen
dc.subject.meshSingle-Cell Analysisen
dc.subject.meshTumor Microenvironmenten
dc.subject.meshTranscriptomeen
dc.subject.meshTumor-Associated Macrophagesen
dc.titleSingle-Cell and Spatial Transcriptomics Reveal a Tumor-Associated Macrophage Subpopulation that Mediates Prostate Cancer Progression and Metastasisen
dc.title.serialMolecular Cancer Researchen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2025-03-14en
pubs.organisational-groupVirginia Techen
pubs.organisational-groupVirginia Tech/All T&R Facultyen
pubs.organisational-groupVirginia Tech/University Research Institutesen
pubs.organisational-groupVirginia Tech/University Research Institutes/Fralin Biomedical Research Institute at VTCen

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