Immune status is prognostic for poor survival in colorectal cancer patients and is associated with tumour hypoxia

Stephanie G. Craig, Matthew P Humphries, Matthew Alderdice, Victoria Bingham, Susan D. Richman, Maurice B. Loughrey, Helen G Coleman, Amelie Viratham-Pulsawatdi, Kris McCombe, Graeme I. Murray, Andrew Blake, Enric Domingo, James Robineau, Louise Brown, David Fisher, Matthew T. Seymour, Phil Quirke, Peter Bankhead, Stephen McQuaid, Mark LawlerDarragh G. McArt, Tim S. Maughan, Jacqueline A James, Manuel Salto-Tellez*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background:
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, FOXP3) and immune checkpoint (ICOS, IDO-1, 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. Additionally, we found immune-cold CRCs to associate with a difficult-to-treat, poor prognosis hypoxia signature indicating these patients may benefit from hypoxia-targeting clinical trials.
Original languageEnglish
JournalBritish Journal of Cancer
Early online date20 Jul 2020
DOIs
Publication statusE-pub ahead of print - 20 Jul 2020

Keywords

  • Cancer microenvironment
  • colorectal cancer
  • tumour biomarkers
  • MICROENVIRONMENT
  • CARCINOMA

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    Craig, S. G., Humphries, M. P., Alderdice, M., Bingham, V., Richman, S. D., Loughrey, M. B., Coleman, H. G., Viratham-Pulsawatdi, A., McCombe, K., Murray, G. I., Blake, A., Domingo, E., Robineau, J., Brown, L., Fisher, D., Seymour, M. T., Quirke, P., Bankhead, P., McQuaid, S., ... Salto-Tellez, M. (2020). Immune status is prognostic for poor survival in colorectal cancer patients and is associated with tumour hypoxia. British Journal of Cancer. https://doi.org/10.1038/s41416-020-0985-5