Human Plasmacytoid Dendritic Cells and Cutaneous Melanoma

Cells. 2020 Feb 11;9(2):417. doi: 10.3390/cells9020417.

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.

Keywords: TLR; cutaneous melanoma; plasmacytoid dendritic cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Humans
  • Immunotherapy
  • Interferon Type I / genetics
  • Interferon Type I / immunology
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • Melanoma / genetics*
  • Melanoma / immunology
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Toll-Like Receptor 7 / genetics*
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 9 / genetics*
  • Toll-Like Receptor 9 / immunology

Substances

  • Interferon Type I
  • TLR7 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MAP Kinase Kinase Kinases