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Eur J Cancer. 2019 Nov 1;123:118-129. doi: 10.1016/j.ejca.2019.09.008. [Epub ahead of print]

The correlation between immune subtypes and consensus molecular subtypes in colorectal cancer identifies novel tumour microenvironment profiles, with prognostic and therapeutic implications.

Author information

1
Laboratorio de Oncología Clínico-Traslacional, Unidad de Investigación en Tumores Digestivos, Instituto de Investigación I+12, Hospital 12 de Octubre, 28041, Madrid, Spain; Centro Nacional de Investigación Oncológica (CNIO), 28029, Madrid, Spain.
2
Bioinformatics Unit, Centro Nacional de Investigación Oncológica (CNIO), 28029, Madrid, Spain.
3
Laboratorio de Oncología Clínico-Traslacional, Unidad de Investigación en Tumores Digestivos, Instituto de Investigación I+12, Hospital 12 de Octubre, 28041, Madrid, Spain; Oncology Department, Hospital Universitario Doce de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), UCM, CNIO, CIBERONC, Madrid, Spain.
4
Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario 12 de Octubre, 28041, Madrid, Spain; Immuno-Oncology and Immunotherapy Group, Instituto de Investigación Sanitaria 12 de Octubre (i+12), 28041, Madrid, Spain; Immunotherapy and Cell Engineering Laboratory, Department of Engineering, Aarhus University, 8000, C Aarhus, Denmark.
5
Laboratorio de Oncología Clínico-Traslacional, Unidad de Investigación en Tumores Digestivos, Instituto de Investigación I+12, Hospital 12 de Octubre, 28041, Madrid, Spain; Oncology Department, Hospital Universitario Doce de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), UCM, CNIO, CIBERONC, Madrid, Spain; Complutense University of Madrid, Madrid, Spain. Electronic address: rgcarbonero@gmail.com.

Abstract

BACKGROUND:

Solid tumour growth is the consequence of a complex interplay between cancer cells and their microenvironment. Recently, a new global transcriptomic immune classification of solid tumours has identified six immune subtypes (ISs) (C1-C6). Our aim was to specifically characterise ISs in colorectal cancer (CRC) and assess their interplay with the consensus molecular subtypes (CMSs).

METHODS:

Clinical and molecular information, including CMSs and ISs, were obtained from The Cancer Genome Atlas (TCGA) (N = 625). Immune cell populations, differential gene expression and gene set enrichment analysis were performed to characterise ISs in the global CRC population by using CMSs.

RESULTS:

Only 5 ISs were identified in CRC, predominantly C1 wound healing (77%) and C2 IFN-γ dominant (17%). CMS1 showed the highest proportion of C2 (53%), whereas C1 was particularly dominant in CMS2 (91%). CMS3 had the highest representation of C3 inflammatory (7%) and C4 lymphocyte depleted ISs (4%), whereas all C6 TGF-β dominant cases belonged to CMS4 (2.3%). Prognostic relevance of ISs in CRC substantially differed from that reported for the global TCGA, and ISs had a greater ability to stratify the prognosis of CRC patients than CMS classification. C2 had higher densities of CD8, CD4 activated, follicular helper T cells, regulatory T cells and neutrophils and the highest M1/M2 polarisation. C2 had a heightened activation of pathways related to the immune system, apoptosis and DNA repair, mTOR signalling and oxidative phosphorylation, whereas C1 was more dependent of metabolic pathways.

CONCLUSIONS:

The correlation of IS and CMS allows a more precise categorisation of patients with relevant clinical and biological implications, which may be valuable tools to improve tailored therapeutic interventions in CRC patients.

KEYWORDS:

Colorectal cancer; Consensus molecular subtypes; Immune subtypes; Immunotherapy; Tumour microenviroment

PMID:
31678770
DOI:
10.1016/j.ejca.2019.09.008
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