Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo

Int J Cancer. 1996 Jul 3;67(1):54-62. doi: 10.1002/(SICI)1097-0215(19960703)67:1<54::AID-IJC11>3.0.CO;2-C.


Peptide epitopes derived from differentiation antigens of the melanocyte lineage were recently identified in human melanomas as targets for MHC-restricted cytotoxic T lymphocytes (CTL). The characterization of multiple CTL-defined antigenic determinants has opened possibilities of development of antigen-targeted vaccines. In the present study, we determined CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase, and gp100/Pmel17 in 3 HLA-A2+ melanoma patients. Then, we assessed the immune responses to synthetic melanoma-associated peptides injected intradermally. After 3 cycles of immunization with peptide alone, we used systemic GM-CSF as an adjuvant during the fourth cycle of immunization. Enhanced DTH reactions and CD8+ CTL responses were observed after treatment with systemic GM-CSF. Immunohistochemical characterization of DTH-constituting elements revealed infiltrates of CD4+ and CD8+ T lymphocytes and strong expression of IL-2 and gammaIFN, suggesting the activation of CD4+ ThI and CD8+ CTL by peptides presented by MHC-class-I molecules of dermal APC. Objective tumor regression was documented in all patients. We conclude that systemic GM-CSF enhances immune responses to melanoma-associated peptides and supports CTL-mediated tumor rejection in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Amino Acid Sequence
  • Antigens, Neoplasm
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Hypersensitivity, Delayed
  • Immunization
  • Immunohistochemistry
  • Male
  • Melanoma / immunology*
  • Melanoma-Specific Antigens
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Proteins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology


  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor