immunoregulation of dendritic cell subsets by inhibitory receptors in urothelial cancer blockade of inhibitory receptors irs overexpressed by t cells can activate antitumor immune responses resulting in the most promising therapeutic approaches particularly in bladder cancer currently able to extend patient survival thanks to their ability to crosspresent antigens to t cells dendritic cells dcs are an immune cell population that plays a central role in the generation of effective antitumor tcell responses while ir function and expression have been investigated in t cells very few data are available for dcs therefore we analyzed whether dcs express irs that can decrease their functions to this end we investigated several irs pd1 ctla4 btla tim3 and cd160 in circulating cd1c dcs cd141 dcs and plasmacytoid dcs from healthy donors and patients with urothelial cancer uca different dc subsets expressed btla and tim3 but not other irs more importantly btla and tim3 were significantly upregulated in dcs from blood of uca patients locally bladder tumorinfiltrating dcs also overexpressed btla and tim3 compared to dcs from paired nontumoral tissue finally in vitro functional experiments showed that ligandmediated engagement of btla and tim3 receptors significantly reduced the secretion of effector cytokines by dc subpopulations our findings demonstrate that uca induces local and systemic overexpression of btla and tim3 by dcs that may result in their functional inhibition highlighting these receptors as potential targets for uca treatmentpatient summary we investigated the expression and function of a panel of inhibitory receptors in dendritic cells dcs an immune cell subpopulation critical in initiation of protective immune responses among patients with urothelial carcinoma we found high expression of btla and tim3 by blood and tumor dcs which could potentially mediate decreased dc function the results suggest that btla and tim3 might be new targets for urothelial carcinoma treatment