Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
Ann N Y Acad Sci. 2013 May;1284:46-51. doi: 10.1111/nyas.12114.
Dendritic cells are master regulators of immunity. Immature dendritic cells are essential for maintaining self-tolerance, while mature dendritic cells initiate a variety of specialized immune responses. Dendritic cell quiescence is often viewed as a default state that requires exogenous stimuli to induce maturation. However, recent studies have identified dendritic cell quiescence factors that actively program dendritic cells to an immature state. In the absence of these factors, dendritic cells spontaneously become immunogenic and can induce autoimmune responses. Herein we discuss two such factors, NF-κB1 and A20, that preserve dendritic cell immaturity through their regulation of NF-κB signaling. Loss of either of these factors increases dendritic cell immunogenicity, suggesting that they may be important targets for enhancing dendritic cell-based cancer immunotherapies. Alternatively, defects in molecules critical for maintaining steady-state DCs may provide novel biomarkers that identify patients who have enhanced natural antitumor immunity or that correlate with better responses to various immunotherapies.
树突状细胞是免疫的主要调节者。未成熟的树突状细胞对于维持自身耐受至关重要，而成熟的树突状细胞则启动各种特异性免疫反应。树突状细胞的静止状态通常被视为一种默认状态，需要外源性刺激来诱导其成熟。然而，最近的研究已经确定了树突状细胞静止状态的调节因子，这些因子可以主动将树突状细胞编程为不成熟状态。在没有这些因子的情况下，树突状细胞会自发地变得具有免疫原性，并可能引发自身免疫反应。在此，我们讨论了两种这样的因子，NF-κB1 和 A20，它们通过调节 NF-κB 信号来维持树突状细胞的不成熟状态。这两种因子中的任何一种缺失都会增加树突状细胞的免疫原性，这表明它们可能是增强基于树突状细胞的癌症免疫疗法的重要靶点。或者，对于维持稳态树突状细胞至关重要的分子的缺陷可能提供新的生物标志物，这些标志物可以识别具有增强的天然抗肿瘤免疫的患者，或者与对各种免疫疗法的更好反应相关。
