GSE131990
Deconvolution of myeloid cell cytokine specific transcriptional profiles during tuberculosis and cancer identifies neutrophil activation as a prognostic feature [cultured cells]
The cytokine environment and cellular infiltrate during an inflammatory response may contain prognostic features that could guide therapy or predict disease outcome. Here we analyzed the transcriptional responses of human monocytes, macrophages, dendritic cells and neutrophils to stimulation by type 1 cytokines (IFN-g, IFN-b and IFN-l) type 2 cytokines (IL-4 and IL-13) and the immunoregulatory cytokine IL-10. This generated a myeloid cell cytokine specific response matrix to infer representation of myeloid cells and the cytokine environment they may encounter during infection and in tumors. Neutrophils were surprisingly responsive to type 1 and type 2 cytokine stimulation but did not respond to IL-10. We identified transcripts specific to IFN-b stimulation, whereas other IFN signature genes were upregulated by both IFN-g and IFN-b. When used to deconvolute blood profiles from tuberculosis patients, the IFN-b specific neutrophil signature was surprisingly reduced in TB patients with active disease whereas the shared response to IFN-g and IFN-b in neutrophils was increased. When applied to glioma patients, transcripts of neutrophils exposed to IL-4 or IL-13 and monocyte responses to IFN-g or IFN-b emerged as opposing predictors of survival in samples from patients with glioma. This approach may help delineate biological roles for myeloid cells in different cytokine environments during disease processes. Overall design: Stimulation of 4 myeloid cell types with 6 cytokines  of 3 anonymous healthy human donors