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Research Article Free access | 10.1172/JCI118958

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.

M J Maeurer, S M Gollin, D Martin, W Swaney, J Bryant, C Castelli, P Robbins, G Parmiani, W J Storkus, and M T Lotze

Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15260, USA.

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Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15260, USA.

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Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15260, USA.

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Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15260, USA.

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Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15260, USA.

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Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15260, USA.

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Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15260, USA.

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Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15260, USA.

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Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15260, USA.

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Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15260, USA.

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First published October 1, 1996 - More info

Published in Volume 98, Issue 7 (October 1, 1996)
J Clin Invest. 1996;98(7):1633–1641. doi:10.1172/JCI118958.
Copyright © 1996, The American Society for Clinical Investigation.

Published October 1, 1996
Abstract

In the last few years, mutiple 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 occurred 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.

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