Abstract
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.
Highlights
The role of plasmacytoid dendritic cells in human pathology has been largely explored, mainly in autoimmune diseases [1]
We review the recent findings on the role of plasmacytoid dendritic cells (pDCs) during melanoma progression, with the proposal to provide the rationale for future treatment options
BDCA-2 cross-linking triggers the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway suppressing the ability of pDCs to produce I interferon (I-IFN) in response to TLR7/9 ligands [63,64,65]
Summary
The role of plasmacytoid dendritic cells (pDCs) in human pathology has been largely explored, mainly in autoimmune diseases [1]. Tumor-associated pDCs have been identified almost two decades ago in solid tumors. Their role during cell transformation and tumor progression is still controversial. We revise novel findings obtained from the recent literature as an extension to previously published reviews on the pDC biology [3,4,5,6,7], development [8], trafficking [9] and on their role in cancer [10,11]. We review the recent findings on the role of pDCs during melanoma progression, with the proposal to provide the rationale for future treatment options
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