PIKfyve控制树突细胞功能和瘤免疫力
Jae Eun Choi1,2, Yuanyuan Qiao1,2,3, Ilona Kryczek4,5
1Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
bioRxiv : the preprint server for biology
|March 11, 2024
概括
向PIKfyve增强树突细胞 (DC) 功能,改善癌症免疫疗法. 抑制PIKfyve增强了DC介导的T细胞免疫力,并增强了免疫检查点阻塞 (ICB) 的有效性,为癌症疫苗提供了新的策略.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 癌症治疗越来越多地使用免疫疗法和向疗法,如蛋白质激酶抑制剂.
- 将向癌症的药物与树突细胞 (DC) 调动和免疫疗法的有效性联系在一起的机制尚不清楚.
研究的目的:
- 研究PIKFYVE基因表达在患者对免疫检查点阻塞 (ICB) 的反应中的作用.
- 探索PIKfyve抑制对DC功能和抗瘤免疫力的影响.
主要方法:
- 分析PIKFYVE表达与癌症患者的ICB反应的关系.
- 在树突细胞中基因切除和药理上抑制PIKfyve.
- 在临床前小鼠模型中评估瘤生长,T细胞免疫力和ICB疗效.
- 对阿皮利莫德 (PIKfyve 抑制剂) 与疫苗辅助剂联合使用的评估.
主要成果:
- 高PIKFYVE表达与较差的ICB完全响应和降低的DC功能相关.
- 在DC中进行PIKfyve切除,通过非正规NF-κB通路增强了它们的功能.
- 抑制PIKfyve (遗传或apilimod) 抑制了瘤生长,并改善了DC依赖的T细胞反应.
- 阿皮利莫德治疗增强了ICB的有效性,并且,与疫苗辅助剂一起,在体内减少了瘤的进展.
结论:
- PIKfyve作为树突细胞功能的负调节剂.
- 抑制PIKfyve显示出增强癌症免疫疗法和疫苗策略的巨大潜力.
关键词:
在 NF-κBB 中.在PIKfyve中使用PIKfyve.抗原特异性T细胞的抗原特异性T细胞.在Apilimod中使用.癌症疫苗 疫苗 癌症疫苗树突细胞的树突细胞.免疫检查点封锁封锁这是一种激酶抑制剂 (kinase inhibitor).瘤是一个瘤.更多相关视频
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