通过抑制可溶性环氧化酶的作用增强癌症免疫疗法
Abigail G Kelly1,2,3, Weicang Wang4,5,6, Eva Rothenberger1,2,3
1Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.
用环氧脂肪酸 (EpFA) 解决炎症可能会改善癌症免疫疗法. 抑制可溶性环氧化酶 (sEH) 增强了EpFAs,增强了抗瘤活性并降低了模型中的毒性.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 癌症免疫疗法,包括免疫检查点抑制 (ICI),由于瘤微环境中的慢性炎症而面临局限性,这可能导致瘤发生和毒性.
- 刺激炎症的缓解是克服这些局限性的潜在策略,并提高癌症治疗的疗效.
- 环氧脂肪酸 (EpFAs) 是能解决炎症的内源调解剂,它们的水平由溶性环氧化酶 (sEH) 调节.
研究的目的:
- 调查调节环氧脂肪酸 (EpFA) 水平是否可以提高免疫检查点抑制 (ICI) 在癌症治疗中的有效性和降低毒性.
- 为了确定抑制可溶性环氧化酶 (sEH) 在ICI治疗期间对瘤微环境和抗瘤免疫反应的影响.
- 探索食脂肪酸补充和药理学SEH抑制作为改善癌症免疫疗法的策略的潜力.
主要方法:
- 用小鼠癌症模型来评估系统性免疫检查点抑制 (ICI) 对可溶性环氧化酶 (sEH) 表达的影响.
- 携带瘤的小鼠接受了食omega-3多不和脂肪酸补充剂和/或药理学sEH抑制剂,单独或与ICI结合治疗.
- 评估了这些干预措施对抗瘤活性,细胞因子概况和瘤微环境的影响.
主要成果:
- 发现系统性免疫检查点抑制 (ICI) 在各种小鼠癌症模型中诱导可溶性环氧化酶 (sEH) 表达.
- 食omega-3脂肪酸补充剂和药理上的SEH抑制,无论是独立的还是与ICI结合的,都显著增强了抗瘤活性.
- 有或没有ICI的sEH途径的药理抑制有效地对抗ICI诱导的促炎和促瘤细胞因子风暴.
结论:
- 调节内源性环氧脂肪酸 (EpFA) 水平是增强免疫检查点抑制 (ICI) 在癌症治疗中的有效性的有希望的策略.
- 抑制可溶性环氧化酶 (sEH) 可以通过缓解炎症和减少有害的细胞因子产生来减轻ICI的不良影响.
- 食补充剂或药理上抑制sEH可能提供一种新的方法来改善癌症免疫治疗患者的结果.
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