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

Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20884-9. doi: 10.1073/pnas.0710557105. Epub 2007 Dec 18.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / blood*
  • CD4-Positive T-Lymphocytes / metabolism
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Interleukin-10 / metabolism
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Melanoma / blood*
  • Melanoma / pathology*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Proteins / biosynthesis
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins / metabolism
  • Survivin
  • T-Lymphocytes, Regulatory / metabolism*
  • Trypsin
  • Trypsinogen / biosynthesis
  • Trypsinogen / metabolism
  • gp100 Melanoma Antigen

Substances

  • Antigens, Neoplasm
  • BIRC5 protein, human
  • CTAG1B protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Inhibitor of Apoptosis Proteins
  • Interleukin-2 Receptor alpha Subunit
  • Membrane Glycoproteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Survivin
  • gp100 Melanoma Antigen
  • Interleukin-10
  • Trypsinogen
  • PRSS1 protein, human
  • Trypsin