Immune cell dysfunctions in breast cancer patients detected through whole blood multi-parametric flow cytometry assay

ABSTRACTMonitoring functional competence of immune cell populations in clinical routine represents a major challenge. We developed a whole-blood assay to monitor functional competence of peripheral innate immune cells including NK cells, dendritic and monocyte cell subsets through their ability to produce specific cytokines after short-term stimulation, detected through intra-cytoplasmic staining and multi-parametric flow-cytometry. A PMA/ionomycin T cell activation assay complemented this analysis. Comparing cohorts of healthy women and breast cancer (BC) patients at different stages, we identified significant functional alteration of circulating immune cells during BC progression prior to initiation of treatment. Of upmost importance, as early as the localized primary tumor (PT) stage, we observed functional alterations in several innate immune populations and T cells i.e. (i) reduced TNFα production by BDCA-1+ DC and non-classical monocytes in response to Type-I IFN, (ii) a strong drop in IFNγ producti...