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pmid:31991796
Tumor Infiltrating Neutrophils Are Enriched in Basal-Type Urothelial Bladder Cancer.
Giulio Eugenio Mandelli · Francesco Missale · Debora Bresciani · Luisa Benerini Gatta · Patrizia Scapini · Elena Caveggion · Elisa Roca · Mattia Bugatti · Matilde Monti · Luca Cristinelli · Sandra Belotti · Claudio Simeone · Stefano Calza · Laura Melocchi · William Vermi
Cells · 2020 doi:10.3390/cells9020291
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy.\nMETHODS: 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.\nRESULTS: 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.\nCONCLUSIONS: 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.", "claims": [{"id": "claim-method", "statement": "Univariate and multivariate survival analyses were performed using Cox proportional hazard models; multivariable models were built by a backward selection applying Likelihood-ratio test and Akaike information criterion; estimates were reported as hazard ratio (HR) with 95% Confidence Intervals (CI95%).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31991796", "locator": "sections[6] \"2.4. 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