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dc.contributor.authorZhang, AW
dc.contributor.authorMcPherson, A
dc.contributor.authorMilne, K
dc.contributor.authorKroeger, DR
dc.contributor.authorHamilton, PT
dc.contributor.authorMiranda, A
dc.contributor.authorFunnell, T
dc.contributor.authorLittle, N
dc.contributor.authorde Souza, CPE
dc.contributor.authorLaan, S
dc.contributor.authorLeDoux, S
dc.contributor.authorCochrane, DR
dc.contributor.authorLim, JLP
dc.contributor.authorYang, W
dc.contributor.authorRoth, A
dc.contributor.authorSmith, MA
dc.contributor.authorHo, J
dc.contributor.authorTse, K
dc.contributor.authorZeng, T
dc.contributor.authorShlafman, I
dc.contributor.authorMayo, MR
dc.contributor.authorMoore, R
dc.contributor.authorFailmezger, H
dc.contributor.authorHeindl, A
dc.contributor.authorWang, YK
dc.contributor.authorBashashati, A
dc.contributor.authorGrewal, DS
dc.contributor.authorBrown, SD
dc.contributor.authorLai, D
dc.contributor.authorWan, ANC
dc.contributor.authorNielsen, CB
dc.contributor.authorHuebner, C
dc.contributor.authorTessier-Cloutier, B
dc.contributor.authorAnglesio, MS
dc.contributor.authorBouchard-Côté, A
dc.contributor.authorYuan, Y
dc.contributor.authorWasserman, WW
dc.contributor.authorGilks, CB
dc.contributor.authorKarnezis, AN
dc.contributor.authorAparicio, S
dc.contributor.authorMcAlpine, JN
dc.contributor.authorHuntsman, DG
dc.contributor.authorHolt, RA
dc.contributor.authorNelson, BH
dc.contributor.authorShah, SP
dc.date.accessioned2018-07-05T08:57:54Z
dc.date.issued2018-06
dc.identifier.citationCell, 2018, 173 (7), pp. 1755 - 1769.e22
dc.identifier.issn0092-8674
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1984
dc.identifier.eissn1097-4172
dc.identifier.doi10.1016/j.cell.2018.03.073
dc.description.abstractHigh-grade serous ovarian cancer (HGSC) exhibits extensive malignant clonal diversity with widespread but non-random patterns of disease dissemination. We investigated whether local immune microenvironment factors shape tumor progression properties at the interface of tumor-infiltrating lymphocytes (TILs) and cancer cells. Through multi-region study of 212 samples from 38 patients with whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T and B cell receptor sequencing, we identified three immunologic subtypes across samples and extensive within-patient diversity. Epithelial CD8+ TILs negatively associated with malignant diversity, reflecting immunological pruning of tumor clones inferred by neoantigen depletion, HLA I loss of heterozygosity, and spatial tracking between T cell and tumor clones. In addition, combinatorial prognostic effects of mutational processes and immune properties were observed, illuminating how specific genomic aberration types associate with immune response and impact survival. We conclude that within-patient spatial immune microenvironment variation shapes intraperitoneal malignant spread, provoking new evolutionary perspectives on HGSC clonal dispersion.
dc.formatPrint-Electronic
dc.format.extent1755 - 1769.e22
dc.languageeng
dc.language.isoeng
dc.subjectLymphocytes, Tumor-Infiltrating
dc.subjectHumans
dc.subjectOvarian Neoplasms
dc.subjectReceptors, Antigen, T-Cell
dc.subjectBRCA1 Protein
dc.subjectBRCA2 Protein
dc.subjectAntigens, Neoplasm
dc.subjectHLA Antigens
dc.subjectCluster Analysis
dc.subjectLoss of Heterozygosity
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectYoung Adult
dc.subjectNeoplasm Grading
dc.subjectWhole Genome Sequencing
dc.subjectCD8 Antigens
dc.titleInterfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer.
dc.typeJournal Article
dcterms.dateAccepted2018-03-27
rioxxterms.versionofrecord10.1016/j.cell.2018.03.073
rioxxterms.licenseref.startdate2018-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell
pubs.issue7
pubs.notesNot known
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
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.publication-statusPublished
pubs.volume173
pubs.embargo.termsNot known
icr.researchteamComputational Pathology & Integrated Genomicsen_US
dc.contributor.icrauthorYuan, Yinyinen


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