Immune status is prognostic for poor survival in colorectal cancer patients and is associated with tumour hypoxia.
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Publication Date
2020-10ICR Author
Author
Craig, SG
Humphries, MP
Alderdice, M
Bingham, V
Richman, SD
Loughrey, MB
Coleman, HG
Viratham-Pulsawatdi, A
McCombe, K
Murray, GI
Blake, A
Domingo, E
Robineau, J
Brown, L
Fisher, D
Seymour, MT
Quirke, P
Bankhead, P
McQuaid, S
Lawler, M
McArt, DG
Maughan, TS
James, JA
Salto-Tellez, M
Type
Conference Proceeding
Metadata
Show full item recordAbstract
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.
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Licenseref URL
http://creativecommons.org/licenses/by/4.0/Version of record
Research team
Integrated Pathology
Date accepted
2020-06-23
License start date
2020-10
Citation
British journal of cancer, 2020, 123 (8), pp. 1280 - 1288