Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma

Luis Vence, A. Karolina Palucka, Joseph W. Fay, Tomoki Ito, Yong Jun Liu, Jacques Banchereau, Hideki Ueno

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

Although it is accepted that regulatory T cells (T regs) contribute to cancer progression, most studies in the field consider nonantigen-specific suppression. Here, we show the presence of tumor antigen-specific CD4 + T regs in the blood of patients with metastatic melanoma. These CD4+ T regs recognize a broad range of tumor antigens, including gp100 and TRP1 (melanoma tissue differentiation antigens), NY-ESO-1 (cancer/testis antigen) and survivin (inhibitor of apoptosis protein (IAP) family antigen). These tumor antigen-specific T regs proliferate in peripheral blood mononuclear cells (PBMC) cultures in response to specific 15-mer peptides, produce preferentially IL-10 and express high levels of FoxP3. They suppress autologous CD4+CD25- T cell responses in a cell contact-dependent manner and thus share properties of both naturally occurring regulatory T cells and type 1 regulatory T cells. Such tumor antigen-specific T regs were not detected in healthy individuals. These tumor antigen-specific T regs might thus represent another target for immunotherapy of metastatic melanoma.

Original languageEnglish
Pages (from-to)20884-20889
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number52
DOIs
StatePublished - 26 Dec 2007
Externally publishedYes

Keywords

  • FoxP3
  • IL-10
  • NY-ESO-1

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