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

British Journal of Cancer
Stephanie G CraigManuel Salto-Tellez

Abstract

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. 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. 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). 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...Continue Reading

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Citations

Aug 13, 2020·Cancers·Erta KalanxhiAnne Hansen Ree
Dec 31, 2020·Cancers·Fatima Abdullahi SidiManuel Salto-Tellez
Feb 19, 2021·Computational and Structural Biotechnology Journal·M P HumphriesM Salto-Tellez
Jun 5, 2021·Cellular and Molecular Gastroenterology and Hepatology·Xin ZhangRong Hu
Jun 27, 2021·NPJ Breast Cancer·Eileen E ParkesNiamh E Buckley
Jul 15, 2021·Cell Communication and Signaling : CCS·Yang SunQiang Zhang
Aug 1, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Rhiannon McShaneMark Bates
Oct 27, 2021·Cancer Biology & Therapy·Vinod S BishtKiran Ambatipudi
Oct 24, 2021·The FEBS Journal·Lizbeth Perez-CastroMaralice Conacci-Sorrell

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Methods Mentioned

BETA
PCR
biopsy

Software Mentioned

R
CRISclassifier
GSEA
Partek® Genomics Suite®
CMSclassifier
QuPath

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