The correlation between immune subtypes and consensus molecular subtypes in colorectal cancer identifies novel tumour microenvironment profiles, with prognostic and therapeutic implications
Entidad
UAM. Departamento de BioquímicaEditor
Elsevier LtdFecha de edición
2019-11-01Cita
10.1016/j.ejca.2019.09.008
European Journal of Cancer 123 (2019): 118-129
ISSN
0959-8049DOI
10.1016/j.ejca.2019.09.008Financiado por
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))Proyecto
Gobierno de España. DTS15/00157; Gobierno de España. PI16/01827; Gobierno de España. CB16/12/00442Versión del editor
https://doi.org/10.1016/j.ejca.2019.09.008Materias
Colorectal cancer; Immune subtypes; Consensus molecular subtypes; Tumour microenviroment; Inmunotherapy; MedicinaDerechos
© 2019 The AuthorsEsta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Resumen
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.
Lista de ficheros
Google Scholar:Soldevilla, B.
-
Carretero-Puche, C.
-
Gómez López, Gonzalo
-
Al-Shahrour, F.
-
Riesco, M. C.
-
Gil-Calderón, B.
-
Alvarez-Vallina, L.
-
Espinosa-Olarte, P.
-
Gómez-Esteves, G.
-
Rubio-Cuesta, B.
-
Sarmentero, J.
-
La Salvia, A.
-
Garcia-Carbonero, R.
Lista de colecciones del ítem
Registros relacionados
Mostrando ítems relacionados por título, autor, creador y materia.
-
Immune subtype in Colorectal Cancer: molecular, functional characterization and clinical implications
Carretero Puche, Carlos
2019-09 -
Author Correction: Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer (Scientific Reports, (2019), 9, 1, (2589), 10.1038/s41598-019-39291-2)
Borrero-Palacios, A.; Cebrián, A.; Gómez del Pulgar, M. T.; García-Carbonero, R.; Garcia-Alfonso, P.; Aranda, E.; Elez, E.; López-López, R.; Cervantes, A.; Valladares, M.; Nadal, C.; Viéitez, J. M.; Guillén-Ponce, C.; Rodríguez, J.; Hernández, I.; García, J. L.; Vega-Bravo, R.; Puime-Otin, A.; Martínez-Useros, J.; Del Puerto-Nevado, L.; Rincón, R.; Rodríguez-Remírez, M.; Rojo, F.; García-Foncillas López, Jesús Miguel; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD)
2019-05-17