Department of Molecular and Translational Medicine, University of Brescia, Brescia 25123, Italy.
Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Medical Oncology, University of Brescia at ASST-Spedali Civili, Brescia 25123, Italy.
Cells. 2020 Feb 11;9(2):417. doi: 10.3390/cells9020417.
The prognosis of metastatic melanoma (MM) patients has remained poor for a long time. However, the recent introduction of effective target therapies (BRAF and MEK inhibitors for BRAFV600-mutated MM) and immunotherapies (anti-CTLA-4 and anti-PD-1) has significantly improved the survival of MM patients. Notably, all these responses are highly dependent on the fitness of the host immune system, including the innate compartment. Among immune cells involved in cancer immunity, properly activated plasmacytoid dendritic cells (pDCs) exert an important role, bridging the innate and adaptive immune responses and directly eliminating cancer cells. A distinctive feature of pDCs is the production of high amount of type I Interferon (I-IFN), through the Toll-like receptor (TLR) 7 and 9 signaling pathway activation. However, published data indicate that melanoma-associated escape mechanisms are in place to hijack pDC functions. We have recently reported that pDC recruitment is recurrent in the early phases of melanoma, but the entire pDC compartment collapses over melanoma progression. Here, we summarize recent advances on pDC biology and function within the context of melanoma immunity.
转移性黑色素瘤 (MM) 患者的预后长期以来一直不佳。然而,最近引入的有效靶向治疗(BRAF 和 MEK 抑制剂用于 BRAFV600 突变 MM)和免疫疗法(抗 CTLA-4 和抗 PD-1)显著改善了 MM 患者的生存。值得注意的是,所有这些反应都高度依赖于宿主免疫系统的适应性,包括先天免疫系统。在涉及癌症免疫的免疫细胞中,适当激活的浆细胞样树突状细胞 (pDC) 发挥着重要作用,它连接先天免疫和适应性免疫反应,并直接消除癌细胞。pDC 的一个显著特征是通过 Toll 样受体 (TLR) 7 和 9 信号通路的激活产生大量 I 型干扰素 (IFN)。然而,已发表的数据表明,黑色素瘤相关的逃逸机制被用来劫持 pDC 的功能。我们最近报道,pDC 的募集在黑色素瘤的早期阶段反复出现,但整个 pDC 区室在黑色素瘤进展过程中崩溃。在这里,我们总结了 pDC 生物学和功能在黑色素瘤免疫中的最新进展。