7月12日,，Cancer Res雜志報(bào)道一類CXCR3+調(diào)節(jié)性T細(xì)胞參與卵巢腫瘤的免疫抑制，這或許成為腫瘤免疫治療的一個(gè)新的靶點(diǎn),。
抗腫瘤的I型T細(xì)胞反應(yīng),，涉及IFN-γ的產(chǎn)生是控制癌癥的關(guān)鍵，但這種反應(yīng)的效率受多種免疫抑制機(jī)制的限制,。這些抑制機(jī)制可促進(jìn)腫瘤免疫逃逸,。其中一項(xiàng)免疫抑制機(jī)制涉及FOXP3+ 調(diào)節(jié)性T細(xì)胞（Treg）的積累。這類抑制性T細(xì)胞可防止過度免疫反應(yīng)造成的組織破壞,。
最近的研究顯示,，F(xiàn)OXP3 +調(diào)節(jié)性T細(xì)胞包括不同亞群，分別發(fā)揮不同的功能,。特別是CXCR3+ Treg細(xì)胞,，已被證明特異性地控制體內(nèi)的I型T細(xì)胞反應(yīng)。本研究發(fā)現(xiàn),，CXCR3+ Treg細(xì)胞高度富集于人類卵巢癌,，特別是在實(shí)體腫瘤中，它們是Treg細(xì)胞的主體,。
體外實(shí)驗(yàn)中,，腫瘤相關(guān)CXCR3+ Treg細(xì)胞共表達(dá)T-bet，但不分泌γ-干擾素,，也不抑制細(xì)胞增殖和T效應(yīng)細(xì)胞的γ-干擾素分泌,。此外，它們共表達(dá)Helios （Helios是人類胸腺衍生FOXP3 +調(diào)節(jié)性T細(xì)胞的標(biāo)記）,，表明它們從天然調(diào)節(jié)性T細(xì)胞起源,。最后，科學(xué)家證實(shí)CXCR3+調(diào)節(jié)性T細(xì)胞在腫瘤部位的比例與CXCR3+T效應(yīng)細(xì)胞直接相關(guān),，與CXCR3的配體表達(dá)一致,。總之,，本研究結(jié)果支持這一概念,，天然CXCR3+/T-bet+調(diào)節(jié)性T細(xì)胞選擇性積聚在卵巢腫瘤組織中，控制I型T細(xì)胞反應(yīng),，導(dǎo)致對(duì)有效抗腫瘤免疫的抑制,。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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CXCR3+ T regulatory cells selectively accumulate in human ovarian carcinomas to limit type I immunity
Nassima Redjimi1,Caroline Raffin1,Isabelle Raimbaud1,Pascale Pignon1,Junko Matsuzaki2,Kunle Odunsi2,Danila Valmori1,*, andMaha Ayyoub
Anti-tumor 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 immunsuppressive 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 co-express T-bet but do not secrete IFN-γ ex vivo and suppress proliferation and IFN-γ secretion of T effectors. In addition, they co-express 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 anti-tumor immunity.
