CXCR3+ T Regulatory Cells Selectively Accumulate in Human Ovarian Carcinomas to Limit Type I Immunity

N Redjimi, C Raffin, I Raimbaud, P Pignon, J Matsuzaki… - Cancer research, 2012 - AACR
N Redjimi, C Raffin, I Raimbaud, P Pignon, J Matsuzaki, K Odunsi, D Valmori, M Ayyoub
Cancer research, 2012AACR
Antitumor type I T-cell responses involving IFN-γ production are critical to control cancer, but
the efficacy of this response is limited by a variety of immunosuppressive mechanisms that
promote tumoral immune escape. One critical mechanism involves the accumulation of
FOXP3+ T regulatory cells (Treg), a class of suppressive T cells that prevent excessive
tissue destruction caused by unchecked immune responses. Recent studies have revealed
that FOXP3+ Treg include distinct subsets specifically controlling over the corresponding …
Abstract
Antitumor type I T-cell responses involving IFN-γ production are critical to control cancer, but the efficacy of this response is limited by a variety of immunosuppressive mechanisms that promote tumoral immune escape. One critical mechanism involves the accumulation of FOXP3+ T regulatory cells (Treg), a class of suppressive T cells that prevent excessive tissue destruction caused by unchecked immune responses. Recent studies have revealed that FOXP3+ Treg include distinct subsets specifically controlling over the corresponding effector subset. In particular, CXCR3+ Treg have been described as a subset specialized in the control of type I T-cell responses in vivo. Here, we show that CXCR3+ Treg are highly enriched in human ovarian carcinomas, particularly in solid tumor masses, where they represent the majority of Treg. Tumor-associated CXCR3+. Treg coexpress T-bet but do not secrete IFN-γ ex vivo and suppress proliferation and IFN-γ secretion of T effectors. In addition, they coexpress Helios, suggesting that they originate from natural Treg. Finally, we show that the proportion of CXCR3+ Treg at tumor sites is directly correlated with that of CXCR3+ T effectors, consistent with expression of CXCR3 ligands. Together, our findings support the concept that natural CXCR3+ T-bet+ Treg selectively accumulate in ovarian tumors to control type I T-cell responses, resulting in the collateral limitation of efficient antitumor immunity. Cancer Res; 72(17); 4351–60. ©2012 AACR.
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