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

Source: https://onco.cc/key-papers/paper-yee-t-cell-vitiligo-jem-2000/  
OnCo record `paper-yee-t-cell-vitiligo-jem-2000` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A report of one patient whose infused melanoma-targeting T cells also attacked normal pigment cells in the skin, which the authors called the first direct evidence in humans that such cells can harm healthy tissue carrying the same protein.

## Summary

A patient with metastatic melanoma developed inflammatory lesions around pigmented areas of skin after an infusion of MART-1-specific CD8+ T-cell clones (Journal of Experimental Medicine 2000). Tetramer analysis showed MART-1-specific CD8+ T cells, identical to the infused clones by CDR3 sequencing, made up more than 28 per cent of CD8 T cells in the skin, and post-infusion biopsies showed loss of MART-1 expression and absence of melanocytes in affected skin (Journal of Experimental Medicine 2000).

## Fields

- Kind: Key paper
- Last checked: 2026-11-05
- Journal: The Journal of Experimental Medicine
- Year: 2000
- DOI: 10.1084/jem.192.11.1637
- Authors: Yee C, Thompson JA, Roche P, Byrd DR, Lee PP, Piepkorn M, Kenyon K, Davis MM, Riddell SR, Greenberg PD.
- Findings: Infused MART-1-specific CD8+ T-cell clones were found at more than 28 per cent of all CD8 T cells in skin lesions, identical to the infused clones.; Post-infusion skin biopsies showed loss of MART-1 expression, melanocyte damage and complete absence of melanocytes in affected regions.
- What it means: Targeting a protein that tumours share with normal cells can damage those normal cells too; the authors state this was the first direct evidence of it in humans, which shaped later thinking on on-target, off-tumour toxicity.
- Caveats: A single patient.

## Sources

- DOI 10.1084/jem.192.11.1637: https://doi.org/10.1084/jem.192.11.1637
- PubMed 11104805: https://pubmed.ncbi.nlm.nih.gov/11104805/

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/)
- institutions: [Fred Hutchinson Cancer Center](https://onco.cc/institutions/fred-hutch/)
- terms: [Endogenous T-cell therapy](https://onco.cc/terms/endogenous-t-cell-therapy/)
- people: [Cassian Yee](https://onco.cc/people/cassian-yee/)

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