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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
乳酸在高糖酵解肿瘤微环境中促进调节性 T 细胞中 PD-1 的表达
英文原题：Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments.
查看英文原题
Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments.
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中文摘要
肿瘤微环境（TME）中表达程序性死亡-1（PD-1）的CD8+ T细胞与调节性T（Treg）细胞之间的平衡，通过二者再激活的竞争决定了PD-1阻断治疗的临床疗效。然而，决定这一平衡的因素仍不清楚。在此，我们表明，在高糖酵解肿瘤（包括MYC扩增肿瘤和肝脏肿瘤）中，Treg细胞比效应T细胞获得更高的PD-1表达。在肿瘤细胞消耗葡萄糖导致的低糖环境下，Treg细胞通过单羧酸转运蛋白1（MCT1）主动吸收乳酸（LA），促进NFAT1易位入核，从而增强PD-1的表达，而效应T细胞的PD-1表达则受到抑制。PD-1阻断激活了表达PD-1的Treg细胞，导致治疗失败。我们提出，高糖酵解TME中的LA通过上调PD-1表达，是TME中Treg细胞功能的一个活跃检查点。
展开英文摘要原文
The balance of programmed death-1 (PD-1)-expressing CD8 + T cells and regulatory T (Treg) cells in the tumor microenvironment (TME) determines the clinical efficacy of PD-1 blockade therapy through the competition of their reactivation.
However, factors that determine this balance remain unknown.
Here, we show that Treg cells gain higher PD-1 expression than effector T cells in highly glycolytic tumors, including MYC-amplified tumors and liver tumors. Under low-glucose environments via glucose consumption by tumor cells, Treg cells actively absorbed lactic acid (LA) through monocarboxylate transporter 1 (MCT1), promoting NFAT1 translocation into the nucleus, thereby enhancing the expression of PD-1, whereas PD-1 expression by effector T cells was dampened. PD-1 blockade invigorated the PD-1-expressing Treg cells, resulting in treatment failure.
We propose that LA in the highly glycolytic TME is an active checkpoint for the function of Treg cells in the TME via upregulation of PD-1 expression.
论文信息
- 作者
- Kumagai S、Koyama S、Itahashi K、Tanegashima T、Lin YT、Togashi Y、Kamada T、Irie T
- 第一作者单位
- Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo 104-0045, Japan; Division of Cancer Immunology, Research Institute/Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo 104-0045/Chiba 277-8577, Japan; Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.Japan
- 通讯作者单位
- Division of Cancer Immunology, Research Institute/Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo 104-0045/Chiba 277-8577, Japan; Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. Electronic address: hnishika@ncc.go.jp.Japan
- 文献类型
- 非美国政府资助研究
- 期刊
- Cancer cell2022 Feb 14
- 原文标识
- PubMed 35090594 · DOI 10.1016/j.ccell.2022.01.001