Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of t cell-mediated vitiligo

• Published in: The Journal of experimental medicine Vol. 192; no. 11; pp. 1637 - 1644
• Main Authors: Yee, C, Thompson, J A, Roche, P, Byrd, D R, Lee, P P, Piepkorn, M, Kenyon, K, Davis, M M, Riddell, S R, Greenberg, P D
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 04-12-2000
• Subjects: Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - immunology; Brief Definitive Report; Female; Humans; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - methods; MART-1 Antigen; Melanocytes - cytology; Melanocytes - immunology; Melanoma - complications; Melanoma - immunology; Melanoma - pathology; Melanoma - therapy; Middle Aged; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - immunology; Skin - cytology; Skin - immunology; Skin - pathology; Skin Neoplasms - complications; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Skin Neoplasms - therapy; T-Lymphocytes, Cytotoxic - classification; T-Lymphocytes, Cytotoxic - immunology; Vitiligo - etiology; Vitiligo - immunology; Vitiligo - pathology
• ISSN: 0022-1007; 1892-1007; 1540-9538
• DOI: 10.1084/jem.192.11.1637

Current strategies for the immunotherapy of melanoma include augmentation of the immune response to tumor antigens represented by melanosomal proteins such as tyrosinase, gp100, and MART-1. The possibility that intentional targeting of tumor antigens representing normal proteins can result in autoimmune toxicity has been postulated but never demonstrated previously in humans. In this study, we describe a patient with metastatic melanoma who developed inflammatory lesions circumscribing pigmented areas of skin after an infusion of MART-1-specific CD8(+) T cell clones. Analysis of the infiltrating lymphocytes in skin and tumor biopsies using T cell-specific peptide-major histocompatibility complex tetramers demonstrated a localized predominance of MART-1-specific CD8(+) T cells (>28% of all CD8 T cells) that was identical to the infused clones (as confirmed by sequencing of the complementarity-determining region 3). In contrast to skin biopsies obtained from the patient before T cell infusion, postinfusion biopsies demonstrated loss of MART-1 expression, evidence of melanocyte damage, and the complete absence of melanocytes in affected regions of the skin. This study provides, for the first time, direct evidence in humans that antigen-specific immunotherapy can target not only antigen-positive tumor cells in vivo but also normal tissues expressing the shared tumor antigen.