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

Autor: Rocio Garcia-Carbonero, Beatriz Gil-Calderón, Gonzalo Gómez-López, A. La Salvia, Fatima Al-Shahrour, Luis Álvarez-Vallina, M.C. Riesco, Carlos Carretero-Puche, J. Sarmentero, Beatriz Soldevilla, B. Rubio-Cuesta, P. Espinosa-Olarte, G. Gomez-Esteves
Přispěvatelé: UAM. Departamento de Bioquímica
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cancer Research
Colorectal cancer
medicine.medical_treatment
Lymphocyte
Consensus molecular subtypes
Genes
MHC Class I
CD8-Positive T-Lymphocytes
Monocytes
Transcriptome
0302 clinical medicine
Transforming Growth Factor beta
Tumor Microenvironment
Lymphocytes
Wnt Signaling Pathway
education.field_of_study
Neovascularization
Pathologic
Inmunotherapy
Prognosis
Adenocarcinoma
Mucinous
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Female
Microsatellite Instability
Immunotherapy
Colorectal Neoplasms
Signal Transduction
Proto-Oncogene Proteins B-raf
Immune subtypes
Epithelial-Mesenchymal Transition
Medicina
Population
Receptors
Antigen
T-Cell
Adenocarcinoma
Proto-Oncogene Proteins c-myc
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
Interferon-gamma
Immune system
Th2 Cells
health services administration
medicine
Humans
education
Aged
Cell Proliferation
Inflammation
Wound Healing
business.industry
Macrophages
Th1 Cells
medicine.disease
030104 developmental biology
Cancer cell
Cancer research
Th17 Cells
business
CD8
Tumour microenviroment
Zdroj: Soldevilla, B, Carretero-Puche, C, Gomez-Lopez, G, Al-Shahrour, F, Riesco, M C, Gil-Calderon, B, Alvarez-Vallina, L, Espinosa-Olarte, P, Gomez-Esteves, G, Rubio-Cuesta, B, Sarmentero, J, La Salvia, A & Garcia-Carbonero, R 2019, ' The correlation between immune subtypes and consensus molecular subtypes in colorectal cancer identifies novel tumour microenvironment profiles, with prognostic and therapeutic implications ', European Journal of Cancer, vol. 123, pp. 118-129 . https://doi.org/10.1016/j.ejca.2019.09.008
Biblos-e Archivo. Repositorio Institucional de la UAM
instname
Biblos-e Archivo: Repositorio Institucional de la UAM
Universidad Autónoma de Madrid
Popis: 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.
This work was funded by projects DTS15/00157 , PI16/01827 and CIBER-ONC CB16/12/00442 from the Instituto de Salud Carlos III ( Ministry of Economy, Industry and Competitiveness, Spain ) and cofunded by the European Regional Development Fund (ERDF, European Union), and approved by the Ethics Committee or our Institution. BS is funded by AECC (Spain). MCR is funded by Instituto de Salud Carlos III and SEOM (Spain) CCP and BRC are funded by CAM (Programa de Empleo Juvenil (YEI))
Databáze: OpenAIRE
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