Dataset related to article "Costimulatory Molecules and Immune Checkpoints Are Differentially Expressed on Different Subsets of Dendritic Cells."

Dendritic cells (DCs) play a crucial role in initiating and shaping immune responses. The effects of DCs on adaptive immune responses depend partly on functional specialization of distinct DC subsets, and partly on the activation state of DCs, which is largely dictated by environmental signals. Fully activated immunostimulatory DCs express high levels of costimulatory molecules, produce pro-inflammatory cytokines, and stimulate T cell proliferation, whereas tolerogenic DCs express low levels of costimulatory molecules, produce immunomodulatory cytokines and impair T cell proliferation. Relevant to the increasing use of immune checkpoint blockade in cancer treatment, signals generated from inhibitory checkpoint molecules on DC surface may also contribute to the inhibitory properties of tolerogenic DCs. Yet, our knowledge on the expression of inhibitory molecules on human DC subsets is fragmentary. Therefore, in this study, we investigated the expression of three immune checkpoints on peripheral blood DC subsets, in basal conditions and upon exposure to pro-inflammatory and anti-inflammatory stimuli, by using a flow cytometric panel that allows a direct comparison of the activatory/inhibitory phenotype of DC-lineage and inflammatory DC subsets. We demonstrated that functionally distinct DC subsets are characterized by differential expression of activatory and inhibitory molecules, and that cDC1s in particular are endowed with a unique immune checkpoint repertoire characterized by high TIM-3 expression, scarce PD-L1 expression and lack of ILT2. Notably, this unique cDC1 repertoire was subverted in a group of patients with myelodysplastic syndromes included in the study. Applied to the characterization of DCs in the tumor microenvironment, this panel has the potential to provide valuable information to be used for investigating the role of DC subsets in cancer, guiding DC-targeting treatments, and possibly identifying predictive biomarkers for clinical response to cancer immunotherapy.树突状细胞（Dendritic cells, DCs）在启动并塑造免疫应答过程中发挥关键作用。DCs对适应性免疫应答（adaptive immune responses）的调控作用，一方面取决于不同DC亚群的功能特化，另一方面则受DCs自身活化状态的影响，而后者在很大程度上由环境信号所决定。完全活化的免疫刺激性DCs可高表达共刺激分子（costimulatory molecules）、分泌促炎细胞因子（pro-inflammatory cytokines），并促进T细胞增殖（T cell proliferation）；而耐受性DCs（tolerogenic DCs）则仅低表达共刺激分子、分泌免疫调节细胞因子，且会削弱T细胞增殖能力。鉴于癌症治疗中免疫检查点阻断疗法（immune checkpoint blockade）的应用日益增多，DC表面的抑制性检查点分子（inhibitory checkpoint molecules）所介导的信号，同样可能参与赋予耐受性DCs的免疫抑制特性。然而，目前我们对于人类DC亚群表面抑制性分子的表达情况认知较为零散。因此，本研究借助可直接比对DC谱系与炎性DC亚群活化/抑制表型的流式细胞术检测组合（flow cytometric panel），探究了基础状态下以及经促炎、抗炎刺激后，外周血DC亚群上三种免疫检查点（immune checkpoint）的表达情况。本研究证实，功能各异的DC亚群其活化与抑制性分子的表达模式存在显著差异；其中cDC1亚群尤为独特，其免疫检查点表达谱呈现高表达TIM-3、低表达PD-L1且不表达ILT2的特征。值得注意的是，本研究纳入的一组骨髓增生异常综合征（myelodysplastic syndromes）患者体内，这种独特的cDC1亚群免疫检查点表达谱发生了异常改变。若将该流式检测组合应用于肿瘤微环境（tumor microenvironment）中DCs的特征分析，其有望为以下研究提供有价值的信息：探究DC亚群在癌症发生发展中的作用、指导靶向DC的治疗方案（DC-targeting treatments），甚至可能为预测癌症免疫治疗（cancer immunotherapy）的临床应答找到相关预测性生物标志物（predictive biomarkers）。