Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients

Clin Cancer Res. 2003 Nov 1;9(14):5091-100.


Purpose: We have investigated the capacity of immature and mature monocyte-derived DCs pulsed with melanoma-associated peptides (gp100 and tyrosinase) to induce a primary cytotoxic T-lymphocyte response in vivo.

Experimental design: Advanced HLA-A2.1(+) melanoma patients were vaccinated with peptide- and keyhole limpet hemocyanin (KLH)-pulsed DCs, either immature (9 patients) or matured by monocyte-conditioned medium/tumor necrosis factor alpha/prostaglandin E(2) (10 patients).

Results: All patients vaccinated with mature DCs showed a pronounced proliferative T-cell and humoral response against KLH. By contrast, KLH responses were absent in most of the patients vaccinated with immature DCs. Delayed-type hypersensitivity (DTH) reactions against antigen-pulsed DCs were only observed in patients vaccinated with mature DCs and not in patients vaccinated with immature DCs. MHC-peptide tetramer staining of DTH-derived T cells revealed the presence of specific T cells recognizing the melanoma-associated peptides in 1 patient. In a second patient, DTH-derived T cells showed specific lysis of tumor cells expressing the antigens used for DC pulsing. Only patients vaccinated with mature DCs showed objective clinical responses. Interestingly, both patients with long-term progression-free survival (22 and >40 months) were both vaccinated with mature DCs and demonstrated antigen-specific T-cell reactivity of DTH-derived T cells.

Conclusions: We conclude that mature DC are superior to immature DC in the induction of immunological responses in melanoma patients, which may translate into improved clinical results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adult
  • Aged
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Division
  • Cytotoxicity, Immunologic / immunology*
  • Dendritic Cells / immunology*
  • Female
  • HLA-A2 Antigen / metabolism
  • Hemocyanins / pharmacology
  • Humans
  • Hypersensitivity, Delayed / immunology
  • Interferon-gamma / metabolism
  • Male
  • Melanoma / immunology*
  • Melanoma / metabolism
  • Melanoma / secondary
  • Membrane Glycoproteins / immunology
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monophenol Monooxygenase / immunology
  • Neoplasm Proteins / immunology
  • Peptide Fragments / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccination
  • gp100 Melanoma Antigen


  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA-A2 Antigen
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Peptide Fragments
  • gp100 Melanoma Antigen
  • Interferon-gamma
  • Hemocyanins
  • Monophenol Monooxygenase
  • keyhole-limpet hemocyanin