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dc.contributor.authorCraig, SG
dc.contributor.authorHumphries, MP
dc.contributor.authorAlderdice, M
dc.contributor.authorBingham, V
dc.contributor.authorRichman, SD
dc.contributor.authorLoughrey, MB
dc.contributor.authorColeman, HG
dc.contributor.authorViratham-Pulsawatdi, A
dc.contributor.authorMcCombe, K
dc.contributor.authorMurray, GI
dc.contributor.authorBlake, A
dc.contributor.authorDomingo, E
dc.contributor.authorRobineau, J
dc.contributor.authorBrown, L
dc.contributor.authorFisher, D
dc.contributor.authorSeymour, MT
dc.contributor.authorQuirke, P
dc.contributor.authorBankhead, P
dc.contributor.authorMcQuaid, S
dc.contributor.authorLawler, M
dc.contributor.authorMcArt, DG
dc.contributor.authorMaughan, TS
dc.contributor.authorJames, JA
dc.contributor.authorSalto-Tellez, M
dc.date.accessioned2020-12-01T16:57:13Z
dc.date.issued2020-10
dc.identifier.citationBritish journal of cancer, 2020, 123 (8), pp. 1280 - 1288
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4249
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/s41416-020-0985-5
dc.description.abstractBackground Immunohistochemical quantification of the immune response is prognostic for colorectal cancer (CRC). Here, we evaluate the suitability of alternative immune classifiers on prognosis and assess whether they relate to biological features amenable to targeted therapy.Methods Overall survival by immune (CD3, CD4, CD8, CD20 and FOXP3) and immune-checkpoint (ICOS, IDO-1 and PD-L1) biomarkers in independent CRC cohorts was evaluated. Matched mutational and transcriptomic data were interrogated to identify associated biology.Results Determination of immune-cold tumours by combined low-density cell counts of CD3, CD4 and CD8 immunohistochemistry constituted the best prognosticator across stage II-IV CRC, particularly in patients with stage IV disease (HR 1.98 [95% CI: 1.47-2.67]). These immune-cold CRCs were associated with tumour hypoxia, confirmed using CAIX immunohistochemistry (P = 0.0009), which may mediate disease progression through common biology (KRAS mutations, CRIS-B subtype and SPP1 mRNA overexpression).Conclusions Given the significantly poorer survival of immune-cold CRC patients, these data illustrate that assessment of CD4-expressing cells complements low CD3 and CD8 immunohistochemical quantification in the tumour bulk, potentially facilitating immunophenotyping of patient biopsies to predict prognosis. In addition, we found immune-cold CRCs to associate with a difficult-to-treat, poor prognosis hypoxia signature, indicating that these patients may benefit from hypoxia-targeting clinical trials.
dc.formatPrint-Electronic
dc.format.extent1280 - 1288
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleImmune status is prognostic for poor survival in colorectal cancer patients and is associated with tumour hypoxia.
dc.typeJournal Article
dcterms.dateAccepted2020-06-23
rioxxterms.versionofrecord10.1038/s41416-020-0985-5
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue8
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/Integrated Pathology
pubs.publication-statusPublished
pubs.volume123
pubs.embargo.termsNot known
icr.researchteamIntegrated Pathologyen_US
dc.contributor.icrauthorSalto-Tellez, Manuelen


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