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氨酸通过聚胺合成调节CD8⁺ T细胞的抗瘤功能

Tian Zhao^1,2, Gillian A Carleton^1,2, Sarah Macpherson^2,3

¹Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.

bioRxiv : the preprint server for biology

|November 19, 2025

概括

氨酸限制 (MR) 可以通过抑制聚胺合成来提升T细胞的功能. 然而,在活体中,持续的MR会损害采用T细胞治疗的疗效,这表明增加氨酸的可用性可能是有益的.

科学领域:

免疫学免疫学免疫学
代谢途径代谢途径
癌症治疗治疗癌症治疗

背景情况:

氨酸对于T细胞激活至关重要.
氨酸限制 (MR) 和免疫检查点阻塞可以增强T细胞功能.
氨酸在采用T细胞治疗中的作用尚不清楚.

研究的目的:

调查 metionin 可用性对 T 细胞功能在采用性 T 细胞治疗中的影响.
探索 metionin 通过哪些机制影响 T 细胞活动 in vitro 和 in vivo.

主要方法:

使用了初级T细胞和小鼠采用T细胞治疗模型.
细胞接受过渡性或持续性氨酸限制 (MR) 或氨酸腺转移酶2A抑制剂 (MAT2Ai) 的治疗.
抗瘤疗效使用卵蛋白 (OVA) 特定的 (OT-I) CD8+ T细胞对EG7-OVA瘤进行了评估.

主要成果:

在体外,短暂的MR或MAT2Ai通过抑制聚胺合成,增加了CD8+T细胞中的IFNγ表达.
持续的MR上调了T细胞耗尽标记in vitro.
在体内,短暂的MR并没有提高抗瘤功效,而持续的MR则加速了瘤的生长.

结论:

过渡性MR通过抑制聚胺合成来增强T细胞的功能in vitro.
氨酸的可用性对于被收养转移的T细胞在体内疗效至关重要.
提高瘤微环境中的氨酸可用性可能会改善收养T细胞治疗的结果.

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