HLA-A(*)0201(+) plasmacytoid dendritic cells provide a cell-based immunotherapy for melanoma patients

J Invest Dermatol. 2012 Oct;132(10):2395-2406. doi: 10.1038/jid.2012.152. Epub 2012 Jun 14.


Several sources of evidence suggest that tumor-specific T cells have the potential to control melanoma tumors. Current active and adoptive therapeutic approaches to elicit such T cells are either not sufficiently clinically efficient or require fastidious processes that impede their extensive clinical use. As plasmacytoid dendritic cells (pDCs) have a crucial role in triggering antitumor immunity especially in melanoma, we explored their potential as a cell-based approach for melanoma immunotherapy. An irradiated human HLA-A(*)0201(+) pDC line loaded with peptides derived from the major melanoma tumor antigens, MelA/MART-1, gp100/pmel17, tyrosinase, and MAGE-A3, was used to trigger functional multi-specific T cells ex vivo from peripheral blood mononuclear cells and tumor-infiltrating lymphocytes from stage I-IV HLA-A(*)0201(+) melanoma patients. pDCs loaded with melanoma-derived peptides promptly induced high levels of melanoma tumor-specific T cells from both sources. pDC-primed central/effector memory antitumor T cells were highly functional as indicated by the specific IFNγ secretion and membrane CD107 expression upon stimulation. Cells also exhibited strong cytotoxicity toward semi-allogeneic melanoma cells and patient-derived tumor cells. The simple design and potent efficacy of this promising approach provides a preclinical basis for the development of a pDC-based vaccine and an alternative means to produce tumor-specific T cells for adoptive cellular immunotherapy in melanoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Line
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • HLA-A2 Antigen / metabolism*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / pathology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma / therapy*
  • Neoplasm Staging
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*


  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Lysosomal-Associated Membrane Protein 1
  • Interferon-gamma