Autoimmune melanocyte destruction is required for robust CD8+ memory T cell responses to mouse melanoma

Katelyn T. Byrne, Anik L. Côté, Peisheng Zhang, Shannon M. Steinberg, Yanxia Guo, Rameeza Allie, Weijun Zhang, Marc S. Ernstoff, Edward J. Usherwood, Mary Jo Turk

Research output: Contribution to journalArticlepeer-review

Abstract

A link between autoimmunity and improved antitumor immunity has long been recognized, although the exact mechanistic relationship between these two phenomena remains unclear. In the present study we have found that vitiligo, the autoimmune destruction of melanocytes, generates self antigen required for mounting persistent and protective memory CD8+ T cell responses to melanoma. Vitiligo developed in approximately 60% of mice that were depleted of regulatory CD4+ T cells and then subjected to surgical excision of large established B16 melanomas. Mice with vitiligo generated 10-fold larger populations of CD8+ memory T cells specific for shared melanoma/melanocyte antigens. CD8+ T cells in mice with vitiligo acquired phenotypic and functional characteristics of effector memory, suggesting that they were supported by ongoing antigen stimulation. Such responses were not generated in melanocyte-deficient mice, indicating a requirement for melanocyte destruction in maintaining CD8+ T cell immunity to melanoma. Vitiligo-associated memory CD8+ T cells provided durable tumor protection, were capable of mounting a rapid recall response to melanoma, and did not demonstrate phenotypic or functional signs of exhaustion even after many months of exposure to antigen. This work establishes melanocyte destruction as a key determinant of lasting melanoma-reactive immune responses, thus illustrating that immune-mediated destruction of normal tissues can perpetuate adaptive immune responses to cancer.

Original languageEnglish (US)
Pages (from-to)1797-1809
Number of pages13
JournalJournal of Clinical Investigation
Volume121
Issue number5
DOIs
StatePublished - May 2 2011

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Fingerprint Dive into the research topics of 'Autoimmune melanocyte destruction is required for robust CD8<sup>+</sup> memory T cell responses to mouse melanoma'. Together they form a unique fingerprint.

Cite this