Tumor Infiltrating Neutrophils Are Enriched in Basal-Type Urothelial Bladder Cancer.
Cells
; 9(2)2020 01 25.
Article
en En
| MEDLINE
| ID: mdl-31991796
ABSTRACT
BACKGROUND:
Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy.METHODS:
By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b+ tumor-associated-neutrophils (TAN) and CD3+ T cells. Bioinformatics analysis of UBC datasets and gene expression analysis of UBC cell lines were additionally performed.RESULTS:
Basal type BC contained a significantly higher density of CD66b+ TAN compared to the luminal type. This finding was validated on TCGA, GSE32894 and GSE124305 datasets by computing a neutrophil signature. Of note, basal-type MIBC display a significantly higher level of chemokines (CKs) attracting neutrophils. Moreover, pro-inflammatory stimuli significantly up-regulate CXCL1, CXCL2 and CXCL8 in 5637 and RT4 UBC cell lines and induce neutrophil chemotaxis. In term of survival, a high density of T celsl and TAN was significantly associated to a better outcome, with TAN density showing a more limited statistical power and following a non-linear predicting model.CONCLUSIONS:
TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Vejiga Urinaria
/
Linfocitos T
/
Neoplasias de los Músculos
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Neutrófilos
Tipo de estudio:
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Aged80
Idioma:
En
Revista:
Cells
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia