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dc.contributor.authorNederlof, I
dc.contributor.authorHajizadeh, S
dc.contributor.authorSobhani, F
dc.contributor.authorRaza, SEA
dc.contributor.authorAbdulJabbar, K
dc.contributor.authorHarkes, R
dc.contributor.authorvan de Vijver, MJ
dc.contributor.authorSalgado, R
dc.contributor.authorDesmedt, C
dc.contributor.authorKok, M
dc.contributor.authorYuan, Y
dc.contributor.authorHorlings, HM
dc.coverage.spatialUnited States
dc.date.accessioned2022-07-12T13:04:08Z
dc.date.available2022-07-12T13:04:08Z
dc.date.issued2022-04-28
dc.identifierARTN 56
dc.identifier10.1038/s41523-022-00416-y
dc.identifier.citationnpj Breast Cancer, 2022, 8 (1), pp. 56 -en_US
dc.identifier.issn2374-4677
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5206
dc.identifier.eissn2374-4677
dc.identifier.eissn2374-4677
dc.identifier.doi10.1038/s41523-022-00416-y
dc.identifier.doi10.1038/s41523-022-00416-y
dc.description.abstractIn estrogen-receptor-positive, HER2-negative (ER+HER2-) breast cancer, higher levels of tumor infiltrating lymphocytes (TILs) are often associated with a poor prognosis and this phenomenon is still poorly understood. Fibroblasts represent one of the most frequent cells in breast cancer and harbor immunomodulatory capabilities. Here, we evaluate the molecular and clinical impact of the spatial patterns of TILs and fibroblast in ER+HER2- breast cancer. We used a deep neural network to locate and identify tumor, TILs, and fibroblasts on hematoxylin and eosin-stained slides from 179 ER+HER2- breast tumors (ICGC cohort) together with a new density estimation analysis to measure the spatial patterns. We clustered tumors based on their spatial patterns and gene set enrichment analysis was performed to study their molecular characteristics. We independently assessed the spatial patterns in a second cohort of ER+HER2- breast cancer (N = 630, METABRIC) and studied their prognostic value. The spatial integration of fibroblasts, TILs, and tumor cells leads to a new reproducible spatial classification of ER+HER2- breast cancer and is linked to inflammation, fibroblast meddling, or immunosuppression. ER+HER2- patients with high TIL did not have a significant improved overall survival (HR = 0.76, P = 0.212), except when they had received chemotherapy (HR = 0.447). A poorer survival was observed for patients with high fibroblasts that did not show a high level of TILs (HR = 1.661, P = 0.0303). Especially spatial mixing of fibroblasts and TILs was associated with a good prognosis (HR = 0.464, P = 0.013). Our findings demonstrate a reproducible pipeline for the spatial profiling of TILs and fibroblasts in ER+HER2- breast cancer and suggest that this spatial interplay holds a decisive role in their cancer-immune interactions.
dc.formatElectronic
dc.format.extent56 -
dc.languageeng
dc.language.isoengen_US
dc.publisherNATURE PORTFOLIOen_US
dc.relation.ispartofnpj Breast Cancer
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectOncology
dc.subjectTUMOR-INFILTRATING LYMPHOCYTES
dc.subjectGENE-EXPRESSION SIGNATURE
dc.subjectHETEROGENEITY
dc.subjectSEGMENTATION
dc.subjectLANDSCAPE
dc.titleSpatial interplay of lymphocytes and fibroblasts in estrogen receptor-positive HER2-negative breast cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2022-03-19
dc.date.updated2022-07-12T09:15:52Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1038/s41523-022-00416-yen_US
rioxxterms.licenseref.startdate2022-04-28
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/35484275
pubs.issue1
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Computational Pathology & Integrated Genomics
pubs.organisational-group/ICR/ImmNet
pubs.publication-statusPublished online
pubs.volume8
icr.researchteamComp Path & Int Genomicsen_US
dc.contributor.icrauthorYuan, Yinyin
icr.provenanceDeposited by Prof Yinyin Yuan on 2022-07-12. Deposit type is initial. No. of files: 1. Files: Spatial interplay of lymphocytes and fibroblasts in estrogen receptor-positive HER2-negative breast cancer.pdf


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