Immune status is prognostic for poor survival in colorectal cancer patients and is associated with tumour hypoxia.
Loading...
Embargo End Date
ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2020-10-13
Date Accepted
2020-06-23
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 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.
Citation
British journal of cancer, 2020, 123 (8), pp. 1280 - 1288
Source Title
Publisher
SPRINGERNATURE
ISSN
0007-0920
eISSN
1532-1827
Collections
Research Team
Integrated Pathology