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

^†Baylor Institute for Immunology Research and Baylor Research Institute, Baylor University, Dallas, TX 75204; and
^‡M. D. Anderson Cancer Center, University of Texas, Houston, TX 77030

Communicated by Robert L. Coffman, Dynavax Technologies, Berkeley, CA, November 6, 2007 (received for review July 7, 2007)

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.

Footnotes

^§To whom correspondence should be addressed at:
Baylor Institute for Immunology Research, Baylor University, 3434 Live Oak, Dallas, TX 75204.
E-mail: hidekiu{at}baylorhealth.edu
Author contributions: L.V., A.K.P., J.W.F., J.B., and H.U. designed research; L.V. performed research; T.I. and Y.-J.L. contributed new reagents/analytic tools; L.V., J.B., and H.U. analyzed data; and L.V., A.K.P., J.B., and H.U. wrote the paper.
The authors declare no conflict of interest.