{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:40:49Z","timestamp":1791405649905,"version":"4.3.3"},"reference-count":24,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,12,4]]},"abstract":"<jats:p>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\u2013specific CD8+ T cell clones. Analysis of the infiltrating lymphocytes in skin and tumor biopsies using T cell\u2013specific peptide\u2013major histocompatibility complex tetramers demonstrated a localized predominance of MART-1\u2013specific CD8+ T cells (&amp;gt;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.<\/jats:p>","DOI":"10.1084\/jem.192.11.1637","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1637-1644","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":357,"title":["Melanocyte Destruction after Antigen-Specific Immunotherapy of Melanoma"],"prefix":"10.1084","volume":"192","author":[{"given":"Cassian","family":"Yee","sequence":"first","affiliation":[{"name":"aClinical Research Division, Fred Hutchinson Cancer Research Center, the"},{"name":"bDepartment of Medicine, University of Washington, Seattle, Washington 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"bDepartment of Medicine, University of Washington, Seattle, Washington 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Roche","sequence":"additional","affiliation":[{"name":"dDepartment of Pathology, Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Byrd","sequence":"additional","affiliation":[{"name":"cDepartment of Surgery, University of Washington, Seattle, Washington 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P.","family":"Lee","sequence":"additional","affiliation":[{"name":"eDepartment of Microbiology and Immunology, Stanford University, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Piepkorn","sequence":"additional","affiliation":[{"name":"bDepartment of Medicine, University of Washington, Seattle, Washington 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Kenyon","sequence":"additional","affiliation":[{"name":"aClinical Research Division, Fred Hutchinson Cancer Research Center, the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M.","family":"Davis","sequence":"additional","affiliation":[{"name":"eDepartment of Microbiology and Immunology, Stanford University, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley R.","family":"Riddell","sequence":"additional","affiliation":[{"name":"aClinical Research Division, Fred Hutchinson Cancer Research Center, the"},{"name":"bDepartment of Medicine, University of Washington, Seattle, Washington 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip D.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"aClinical Research Division, Fred Hutchinson Cancer Research Center, the"},{"name":"bDepartment of Medicine, University of Washington, Seattle, Washington 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,12,4]]},"reference":[{"key":"2023072509193432000_R1","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1001\/archderm.1987.01660320095019","article-title":"Prognostic significance of hypopigmentation in malignant melanoma","volume":"123","author":"Bystryn","year":"1987","journal-title":"Arch. 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