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卵巢癌浸润性调节性T细胞比其外周对应细胞更能有效抑制CD8(+) T细胞炎症,这一功能依赖于TIM3表达。

Ovarian carcinoma-infiltrating regulatory T cells were more potent suppressors of CD8(+) T cell inflammation than their peripheral counterparts, a function dependent on TIM3 expression.

作者信息

Bu Meimei, Shen Yizhen, Seeger William L, An Shizhi, Qi Rongqin, Sanderson Joanna A, Cai Yan

机构信息

Department of Anesthesiology, The Maternal and Child Health Hospital of Jinan City, Jinan, Shandong, 250001, China.

Department of Urology, General Hospital of Jinan Military Command, Jinan, Shandong, 250031, China.

出版信息

Tumour Biol. 2016 Mar;37(3):3949-56. doi: 10.1007/s13277-015-4237-x. Epub 2015 Oct 19.

Abstract

Ovarian carcinoma is one of the most severe cancers in women, with a high relapse rate and limited secondary treatment options. To assist research in novel treatment technologies, including CD8(+) T cell-base immunotherapy, we examined the effect of tumor-infiltrating regulatory T cells (Tregs) in inhibiting CD8(+) T cell inflammation. We found that compared to their peripheral blood counterparts, tumor-infiltrating Tregs exhibited more potent inhibitory function, which was associated with higher interleukin 10 (IL-10) production in tumor-infiltrating Tregs. Blockade of T cell immunoglobulin mucin 3 (TIM3), a regulatory molecule overrepresented on tumor-infiltrating Tregs, had significantly reverted Treg-mediated suppression. Moreover, expression of TIM3 on tumor-infiltrating Tregs was directly correlated with tumor size. Together, our results demonstrated that ovarian tumor-infiltrating Treg cells were more immunosuppressive than their peripheral blood counterparts in a TIM3-dependent fashion.

摘要

卵巢癌是女性最严重的癌症之一,复发率高且二线治疗选择有限。为了助力包括基于CD8(+) T细胞的免疫疗法在内的新型治疗技术的研究,我们研究了肿瘤浸润调节性T细胞(Tregs)在抑制CD8(+) T细胞炎症方面的作用。我们发现,与外周血中的Tregs相比,肿瘤浸润性Tregs表现出更强的抑制功能,这与肿瘤浸润性Tregs中更高的白细胞介素10(IL-10)产生有关。阻断T细胞免疫球蛋白粘蛋白3(TIM3),一种在肿瘤浸润性Tregs上过度表达的调节分子,可显著逆转Treg介导的抑制作用。此外,肿瘤浸润性Tregs上TIM3的表达与肿瘤大小直接相关。总之,我们的结果表明,卵巢肿瘤浸润性Treg细胞在TIM3依赖的方式下比外周血中的Treg细胞具有更强的免疫抑制作用。

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