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

L Vence, AK Palucka, JW Fay, T Ito… - Proceedings of the …, 2007 - National Acad Sciences
L Vence, AK Palucka, JW Fay, T Ito, YJ Liu, J Banchereau, H Ueno
Proceedings of the National Academy of Sciences, 2007National Acad Sciences
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 …
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.
National Acad Sciences