Circulating immune cells exhibit distinct traits linked to metastatic burden in breast cancer

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dc.contributor.authorMangiola, S.
dc.contributor.authorBrown, R.
dc.contributor.authorZhan, C.
dc.contributor.authorBerthelet, J.
dc.contributor.authorGuleria, S.
dc.contributor.authorLiyanage, C.
dc.contributor.authorOstrouska, S.
dc.contributor.authorWilcox, J.
dc.contributor.authorMerdas, M.
dc.contributor.authorFuge-Larsen, P.
dc.contributor.authorBell, C.
dc.contributor.authorSchröder, J.
dc.contributor.authorMielke, L.A.
dc.contributor.authorMariadason, J.M.
dc.contributor.authorTsao, S.C.-H.
dc.contributor.authorChen, Y.
dc.contributor.authorYadav, V.K.
dc.contributor.authorVodala, S.
dc.contributor.authorAnderson, R.L.
dc.contributor.authorMerino, D.
dc.contributor.authoret al.
dc.date.issued2025
dc.description.abstractBackground Circulating immune cells play a crucial role in the anti-tumour immune response, yet the systemic immune system in metastatic breast cancers is not fully characterised. Investigating the cellular and molecular changes in peripheral blood mononuclear cells (PBMCs) from breast cancer patients could elucidate the role of circulating immune cells in metastasis and aid in identifying biomarkers for disease burden and progression. Methods In this study, we characterised the systemic immune landscape associated with varying levels of metastatic burden by analysing the single-cell transcriptomes of PBMCs from breast cancer patients and healthy controls. Our research focused on identifying changes in immune cell composition, transcriptional programs, and immune-cell communication networks linked to metastatic burden. Additionally, we compared these PBMC features onto a single-cell atlas of primary breast tumours to study corresponding traits in tumour-infiltrating immune cells. Results In metastatic breast cancer, PBMCs exhibit a significant downregulation of the adaptive immune system and a decreased number and activity of unconventional T cells, such as γδ T cells. Additionally, metastatic burden is associated with impaired cell communication pathways involved in immunomodulatory functions. We also identified a gene signature derived from myeloid cells shared between tumour immune infiltrates and circulating immune cells in breast cancer patients. Conclusions Our study provides a comprehensive single-cell molecular profile of the peripheral immune system in breast cancer, offering a valuable resource for understanding metastatic disease in terms of tumour burden. By identifying immune traits linked to metastasis, we have unveiled potential new biomarkers of metastatic disease.
dc.description.statementofresponsibilityS. Mangiola, R. Brown, C. Zhan, J. Berthelet, S. Guleria, C. Liyanage, S. Ostrouska, J. Wilcox, M. Merdas, P. Fuge-Larsen, C. Bell, J. Schröder, L. A. Mielke, J. M. Mariadason, S. Chang-Hao Tsao, Y. Chen, V. K. Yadav, S. Vodala, R. L. Anderson, D. Merino, A. Behren, B. Yeo, A. T. Papenfuss, B. Pal
dc.identifier.citationBreast Cancer Research, 2025; 27(1):73-1-73-17
dc.identifier.doi10.1186/s13058-025-01982-2
dc.identifier.issn1465-5411
dc.identifier.issn1465-542X
dc.identifier.orcidMangiola, S. [0000-0001-7474-836X]
dc.identifier.orcidZhan, C. [0000-0002-4794-8339]
dc.identifier.urihttps://hdl.handle.net/2440/147760
dc.language.isoen
dc.publisherBMC
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2012196
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1116955
dc.rights© The Author(s) 2025, corrected publication 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttps://doi.org/10.1186/s13058-025-01982-2
dc.subjectPBMCs; breast cancer; metastasis; single-cell RNA sequencing
dc.subject.meshLeukocytes, Mononuclear
dc.subject.meshLymphocytes, Tumor-Infiltrating
dc.subject.meshBreast Neoplasms
dc.subject.meshNeoplasm Metastasis
dc.subject.meshGene Expression Profiling
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshSingle-Cell Analysis
dc.subject.meshTumor Microenvironment
dc.subject.meshTranscriptome
dc.subject.meshBiomarkers, Tumor
dc.titleCirculating immune cells exhibit distinct traits linked to metastatic burden in breast cancer
dc.typeJournal article
pubs.publication-statusPublished

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