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耗尽的T细胞的功能障碍是由MCT11介导的乳酸代谢强制执行的
Ronal M Peralta1,2, Bingxian Xie1,2, Konstantinos Lontos2,3
1Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
Nature immunology
|November 8, 2024
概括
终极耗尽的CD8+ T细胞 (Tex) 调高单碳酸盐输送体11 (MCT11) 以利用瘤微环境乳酸. 准MCT11可以增强T细胞功能,减少瘤生长.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 代谢途径 代谢途径
背景情况:
- CD8+ T 细胞对于抗瘤免疫是至关重要的,但在瘤微环境 (TME) 中会耗尽.
- T细胞疲劳的特征是共抑制分子的上调和功能受损.
- TME呈现出一种代谢性免疫抑制环境,营养素和氧气有限,乳酸盐水平高.
研究的目的:
- 为了研究代谢途径在终极耗尽的T细胞中的作用.
- 为了确定参与耗尽的T细胞吸收营养的特定载体.
- 探索针对耗尽的T细胞代谢脆弱性的治疗策略.
主要方法:
- 对终极耗尽的T细胞中的基因表达的分析.
- 在T细胞中条件删除Slc16a11 (编码为MCT11).
- 在体内研究中,使用与抗MCT11抗体治疗的携带瘤的小鼠.
主要成果:
- 最终耗尽的T细胞独特地调节单碳酸盐载体11 (MCT11).
- 在T细胞中MCT11的缺失减少了乳酸摄取,并改善了效应器功能.
- 抗体介导的MCT11向降低了Tex细胞的乳酸摄取,并抑制了小鼠的瘤生长.
结论:
- 在Tex细胞上调MCT11,使他们能够利用乳酸在TME.
- MCT11代表了恢复抗瘤免疫力的潜在治疗标.
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