由CD11c阳性细胞表达的PIKfyve可以控制瘤免疫力
Jae Eun Choi1,2,3, Yuanyuan Qiao1,2,4, Ilona Kryczek5,6
1Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Nature communications
|June 28, 2024
概括
抑制PIKfyve可以增强树突细胞 (DC) 功能,改善癌症免疫疗法和疫苗疗效. 通过增强抗瘤免疫力,PIKfyve向提供了一种有前途的癌症治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 癌症治疗正在向向治疗的方向发展,如蛋白激酶抑制剂和免疫治疗.
- 树突细胞 (DCs) 对于抗原呈现和杀死癌细胞至关重要,代表了一个未充分利用的治疗点.
- 在DC中高PIKFYVE基因表达与免疫检查点阻塞 (ICB) 治疗的反应不佳相关.
研究的目的:
- 研究PIKFYVE在调节髓状细胞功能的作用,特别是树突细胞 (DCs).
- 评估PIKFYVE抑制在癌症免疫疗法和疫苗策略中的治疗潜力.
主要方法:
- 在CD11c+细胞 (主要是DCs) 中基因切除Pikfyve.
- 使用apilimod进行PIKfyve的药理抑制.
- 在小鼠模型中评估瘤生长,T细胞免疫力和ICB疗效.
- 用疫苗辅助剂和apilimod进行组合治疗的研究.
主要成果:
- 通过调节非正规NF-κB通路,PIKfyve的消去或抑制增强了CD11c+细胞功能.
- 在CD11c+细胞中的Pikfyve损失和apilimod治疗减少了瘤生长,并改善了DC依赖T细胞免疫力.
- 抑制PIKfyve增强了免疫检查点阻塞 (ICB) 治疗的疗效.
- 将阿皮利莫德与疫苗辅助剂结合使用,可在体内减少瘤进展.
结论:
- PIKfyve 作为 CD11c+ 细胞功能的负调节剂.
- 抑制PIKFYVE是一种增强癌症免疫疗法的有希望的策略,包括ICB和基于疫苗的治疗方法.
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