El Marsafy Sanaa, Bagot Martine, Bensussan Armand, Mauviel Alain
INSERM U 697, Paris, France.
Pigment Cell Melanoma Res. 2009 Feb;22(1):30-41. doi: 10.1111/j.1755-148X.2008.00532.x. Epub 2008 Nov 27.
Melanoma is an aggressive malignancy with poor prognosis. Eradication of tumor cells requires an effective interaction between melanoma cells and different players of the immune system. As the most potent professional antigen-presenting cells, dendritic cells (DCs) play a pivotal role in mounting a specific immune response where their intratumoral and peritumoral density as well as their functional status are correlated with clinical staging of the disease and with patients' survival. Under steady-state conditions, internalization of apoptotic cells by immature DCs designates a state of tolerance to self-antigens. Nevertheless, pathogens and necrotic cells interacting with pattern recognition receptors trigger downstream signaling pathways that evoke maturation of DCs, leading to the production of pro-inflammatory cytokines. These mature DCs are essential for T-cell priming and subsequent development of a specific immune response. Altered functions of DCs have an impact on the development of various disorders including autoimmune diseases and cancers. Herein, we focus on the checkpoints created throughout DCs antigen capturing and presentation to T cells, with subsequent development of either tolerance or immune response, with an emphasis on the role played by DCs in melanoma tumorigenesis and their therapeutic potential.
黑色素瘤是一种侵袭性恶性肿瘤，预后较差。根除肿瘤细胞需要黑色素瘤细胞与免疫系统的不同参与者之间进行有效的相互作用。作为最强大的专职抗原呈递细胞，树突状细胞（DCs）在引发特异性免疫反应中起关键作用，其肿瘤内和肿瘤周围的密度以及功能状态与疾病的临床分期和患者的生存率相关。在稳态条件下，未成熟DCs内化凋亡细胞表明对自身抗原处于耐受状态。然而，病原体和坏死细胞与模式识别受体相互作用会触发下游信号通路，引发DCs的成熟，导致促炎细胞因子的产生。这些成熟的DCs对于T细胞启动和随后特异性免疫反应的发展至关重要。DCs功能的改变会影响包括自身免疫性疾病和癌症在内的各种疾病的发展。在此，我们关注在DCs捕获抗原并呈递给T细胞的整个过程中产生的检查点，以及随后耐受或免疫反应的发展，重点是DCs在黑色素瘤肿瘤发生中的作用及其治疗潜力。
