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氨酸-lysophosphatidylcholine抑制了由于免疫检查点阻塞导致的与免疫相关的不良事件

Ian T Mathews^1,2, Priyanka Saminathan¹, Mir Henglin³

¹La Jolla Institute for Immunology, La Jolla, CA 92037.

medRxiv : the preprint server for health sciences

|August 16, 2024

概括

氨酸-lysophosphatidylcholine (LPC 18:2) 是一种循环脂质,有助于在免疫检查点阻塞 (ICB) 癌症治疗期间预防严重的免疫相关不良事件 (irAEs). 补充LPC 18:2可以通过减少炎症来改善患者的结果.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
代谢学代谢学代谢学

背景情况:

免疫检查点阻塞 (ICB) 治疗对于癌症治疗至关重要,但可能导致与免疫相关的不良事件 (irAEs).
介导ICB诱导的IRAE的特定循环因素尚未得到充分理解.
识别这些介质对于改善患者安全和治疗疗效至关重要.

研究的目的:

为了确定与免疫检查点阻塞 (ICB) 治疗相关的免疫相关不良事件 (irAEs) 的循环调解者.
调查林诺-溶酸胆 (LPC 18:2) 在调节ICB-irAEs中的作用.
探索LPC 18:2补充作为治疗策略的潜力.

主要方法:

采用非向质谱法来识别循环中的脂质介质.
对接受ICB治疗固体瘤的三个独立人群的分析.
我们使用了ICB诱导的irrAEs的临床前模型.
对LPC18:2水平,中性恋和irAE发展之间的相关性分析.

主要成果:

在循环中流通的利诺利奥尔-lysophosphatidylcholine (LPC 18:2) 被确定为ICB-irAEs的关键调节器.
在人体研究中,循环中的LPC 18:2水平的下降先于严重的irAEs的出现.
低LPC 18: 2与健康个体和患有严重irAEs的患者中性友好性增加相关.
在临床前模型中,用LPC 18:2进行体内补充可以减少中性恋和组织炎症,而不会影响抗瘤免疫力.

结论:

循环LPC 18:2在人类ICB相关不良事件中起抑制作用.
在ICB治疗期间,LPC 18:2补充显示了预防ICB治疗期间严重炎症的潜力.
这种方法可以通过减轻irAEs而提高ICB治疗结果,同时保持抗瘤反应.

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