The melanoma inhibitor of apoptosis protein: a target for spontaneous cytotoxic T cell responses

J Invest Dermatol. 2004 Feb;122(2):392-9. doi: 10.1046/j.0022-202X.2004.22242.x.


The identification of tumor antigens which expression is essential for the survival of tumor cells is a new avenue to prevent antigen loss variants emerging due to immunoselection, particularly during immune therapy. The melanoma inhibitor of apoptosis protein, ML-IAP (also named livin) counteracts apoptosis induced by death receptors, hypooxgenic conditions, or chemotherapeutic agents. Thus, elevated expression of ML-IAP renders melanoma cells resistant to apoptotic stimuli and thereby potentially contributes to the oncogenic phenotype. Here, we demonstrate that T cells in a large proportion of melanoma patients infiltrating the tumor or circulating in the peripheral blood specifically recognize ML-IAP-derived peptides. Interestingly, the responses against the peptide epitope ML-IAP280-289 were not restricted to melanoma patients but present among peripheral blood T cells in a few healthy controls. In situ peptide/HLA-A2 multimer staining, however, confirmed the infiltration of ML-IAP-reactive cells into the tumor microenvironment. Moreover, ML-IAP-reactive T cells isolated by magnetic beads coated with peptide/HLA-A2 complexes were cytotoxic against HLA-matched melanoma cells. In conclusion, out data strongly indicate ML-IAP as a suitable target for immunologic intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Carrier Proteins / metabolism*
  • HLA-A2 Antigen / metabolism
  • Humans
  • Immunomagnetic Separation
  • Inhibitor of Apoptosis Proteins
  • Melanoma / immunology*
  • Melanoma / metabolism
  • Neoplasm Proteins / metabolism*
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Protein Binding / immunology
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / metabolism
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism


  • Adaptor Proteins, Signal Transducing
  • BIRC7 protein, human
  • Carrier Proteins
  • HLA-A2 Antigen
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins
  • Peptide Fragments