Tumor Infiltrating Neutrophils Are Enriched in Basal-Type Urothelial Bladder Cancer

• Published in: Cells (Basel, Switzerland) Switzerland), 2020-01, Vol.9 (2), p.291
• Main Authors: Mandelli, Giulio Eugenio, Missale, Francesco, Bresciani, Debora, Gatta, Luisa Benerini, Scapini, Patrizia, Caveggion, Elena, Roca, Elisa, Bugatti, Mattia, Monti, Matilde, Cristinelli, Luca, Belotti, Sandra, Simeone, Claudio, Calza, Stefano, Melocchi, Laura, Vermi, William
• Format: Article
• Language: English
• Subjects: basal; bladder cancer; cd3; cd66b; tumor-associated neutrophils
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9020291

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. 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. 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. 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.