向酸胺酶可以增强结肠直肠癌的抗瘤免疫反应
Yadu Vijayan1, Shirley James2, Arun Viswanathan1
1Cancer Research Program, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, 695014, India; Manipal Academy of Higher Education (MAHE), Manipal, 576104, India.
Journal of advanced research
|December 23, 2023
概括
向酸胺酶 (ASAH1) 在结直肠癌 (CRC) 治疗方面显示出前景. 抑制ASAH1诱导癌细胞死亡并增强免疫疗法,减少瘤并激活免疫细胞以获得更好的抗癌反应.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 免疫治疗是一种免疫疗法.
背景情况:
- 酸胺酶 (ASAH1) 参与脂代谢,在某些癌症中过度表达.
- ASAH1在结直肠癌 (CRC) 进展和治疗耐药性的特定作用尚不清楚.
研究的目的:
- 为了研究ASAH1在结直肠癌 (CRC) 进展中的功能.
- 为了确定ASAH1抑制对检查点抑制剂治疗的反应的影响.
主要方法:
- 在人类和小鼠CRC细胞系中利用了ASAH1的药理和遗传沉默.
- 在小鼠模型中进行了体内研究,并在合成CRC模型中测试了ASAH1抑制剂与抗PD-1治疗相结合.
- 进行了转录组和代谢组分析,以阐明ASAH1沉默的影响.
主要成果:
- ASAH1在人体CRC中过度表达;其沉默诱导免疫细胞死亡 (ICD) 和线粒体应激.
- 通过激活I/II型干扰素反应,M1巨细胞和T细胞,单独或与抗PD-1降低瘤的ASAH1抑制 (LCL-521).
- 在组合治疗中观察到增强的细胞毒性T细胞透和显著的抗瘤反应.
结论:
- 在结直肠癌 (CRC) 中,ASAH1 是一种可用药物的标.
- 与ASAH1抑制剂和检查点抑制剂的联合治疗可以增强抗瘤免疫力.
- 抑制ASAH1代表了CRC的潜在治疗策略.
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