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Sarah J McPhedran^1,2, Gillian A Carleton^1,2, Julian J Lum^3,4

¹Trev and Joyce Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada.

Nature metabolism

|February 22, 2024

概括

通过途径级代谢重编程的工程T细胞可以提高它们对固体瘤的有效性. 这种方法解决了瘤微环境中的代谢挑战,改善了T细胞功能和癌症治疗的持久性.

科学领域:

免疫学免疫学免疫学
代谢工程是代谢工程.
癌症治疗癌症治疗

背景情况:

基于T细胞的疗法在固体瘤中表现出有限的有效性,这是由于瘤微环境具有代谢挑战性.
目前的策略集中在单基因操纵上,这不足以克服瘤诱导的免疫抑制.

研究的目的:

审查对固体瘤中T细胞功能至关重要的代谢途径.
探索途径级代谢工程策略,以增强仿真抗原受体T细胞疗法.
确定这些方法临床实施的挑战.

主要方法:

对T细胞代谢和瘤微环境相互作用的基础研究的综述.
对基因组编辑和代谢工程策略的分析.
对临床翻译挑战的讨论.

主要成果:

固体瘤对T细胞施加了显著的代谢压力,限制了它们的抗瘤活性.
途径级代谢工程提供了一个比单基因目标更全面的战略.
已经确定了支持T细胞细胞毒性和持久性的关键代谢途径.

结论:

在途径水平上的代谢工程是改进基于T细胞的癌症疗法的有希望的策略.
解决代谢网络和T细胞功能之间的复杂相互作用对于临床成功至关重要.
需要进一步的研究,以克服将这些策略转化为临床实践的挑战.

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