HLA-A(*)0201(+) plasmacytoid dendritic cells provide a cell-based immunotherapy for melanoma patients.
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.
Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France. Electronic address: carolineaspord@yahoo.com.
Caroline
C
Aspord
University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; Department of Dermatology, Michallon Hospital, Pôle Pluridisciplinaire de Médecine, Grenoble, France.
Marie-Therese
MT
Leccia
University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; Anatomo-cytopathology, Michallon Hospital, Grenoble, France.
Dimitri
D
Salameire
Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France.
David
D
Laurin
Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France.
Laurence
L
Chaperot
University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; Department of Dermatology, Michallon Hospital, Pôle Pluridisciplinaire de Médecine, Grenoble, France.
Julie
J
Charles
Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; University College London, Cancer Institute, London, UK.
Joel
J
Plumas
D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D052118:Lysosomal-Associated Membrane Protein 1; D007371:Interferon-gamma