基酸是抗瘤T细胞反应的代谢检查点
Ping-Chih Ho1, Jessica Dauz Bihuniak2, Andrew N Macintyre3
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
Cell
|September 1, 2015
概括
通过增加基酸 (PEP) 产生的瘤透T细胞的代谢重编程可以增强抗瘤免疫力. 在T细胞中过度表达PCK1可以增强它们的效应器功能,限制瘤生长并改善小鼠的存活率.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞代谢 细胞代谢
- 癌症生物学 癌症生物学
背景情况:
- 激活的T细胞依靠有氧糖解和合成代谢来实现最佳功能.
- 瘤微环境通常缺乏葡萄糖,可能限制T细胞代谢和抗瘤活性.
研究的目的:
- 为了研究糖溶性代谢物酸 (PEP) 在瘤微环境中的T细胞功能中的作用.
- 探索作为免疫疗法策略的瘤反应性T细胞的代谢重编程.
主要方法:
- 研究了PEP对T细胞受体介导的信号和效应器功能的影响.
- 在瘤特异性T细胞中过度表达基酸碳酸酶1 (PCK1),以增加PEP的产生.
- 在患有黑色素瘤的小鼠中评估PCK1-过度表达T细胞的抗瘤疗效.
主要成果:
- 发现烯酸 (PEP) 通过抑制sarco/ER Ca2+-ATPase (SERCA) 来维持T细胞受体介导的信号和效应器功能.
- 在瘤特异性CD4和CD8T细胞中PCK1的过度表达增强了它们的效应器功能.
- 在临床前模型中,PCK1工程T细胞显示出显著的瘤生长限制和延长存活时间.
结论:
- 代谢重编程,特别是通过PCK1增加PEP的产生,可以增强抗瘤T细胞的反应.
- 这项研究确定了T细胞活动的新型代谢检查点,并建议代谢操纵作为一种有前途的免疫治疗方法.
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