Tumor escape from immune recognition: Lethal recurrent melanoma in a patient associated with downregulation of the peptide transporter protein TAP-1 and loss of expression of the immunodominant MART-1/Melan-A antigen

Markus J. Maeurer, Susanne M. Gollin, Dina Martin, William Swaney, John Bryant, Chiara Castelli, Paul Robbins, G. Parmiani, Walter J. Storkus, Michael T. Lotze

Research output: Contribution to journalArticlepeer-review

216 Scopus citations

Abstract

In the last few years, multiple protein target antigens for immunorecognition by T cells have been identified on human melanoma. How melanoma lesions escape from functional antigen-specific immune recognition remains poorly understood. We have identified the concomitant loss of the immunodominant T cell-defined MART-1/Melan-A antigen and downregulation of the TAP-1 gene in a recurrent metastatic melanoma that was resected in 1993. This phenotype was not observed for an earlier autologous melanoma lesion resected in 1987. The 'antigen loss' could be restored in the variant tumor cell line by simultaneously providing both the MART-1/Melan-A gene (by retroviral transfer) and the TAP-1 gene (by a bioballistic approach) resulting in tumor cell sensitivity to MART-1/Melan-A-specific cytotoxic T lymphocytes. This suggests that tumor escape from immune surveillance may have occured in vivo as a sequential result of (a) antigen loss, and (b) downregulation of the peptide-transporter protein TAP-1 expression by this patient's tumor over a 6-yr period from 1987 to 1993. These results suggest that the characterization of the T cell response to melanoma in individual patients and definition of the immunologically relevant genetic defects in tumors may be required to select the most effective therapeutic strategies for a given patient.

Original languageEnglish (US)
Pages (from-to)1633-1641
Number of pages9
JournalJournal of Clinical Investigation
Volume98
Issue number7
DOIs
StatePublished - Oct 1 1996
Externally publishedYes

Keywords

  • T cell recognition
  • TAP
  • antigen processing
  • human melanoma
  • tumor antigens

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