长时间的阿片类药物暴露调节了清细胞细胞癌的分子代谢
Mamatha Garige1, Sarah Poncet1, Alexis Norris2
1Division of Biotechnology Review and Research 1, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
Life (Basel, Switzerland)
|May 27, 2023
概括
在清细胞细胞癌 (ccRCC) 患者中,长期使用阿片类药物会改变瘤代谢和免疫细胞概况. 这种转变影响有氧糖解,表明对ccRCC治疗反应的潜在影响.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 代谢研究研究 代谢研究
背景情况:
- 阿片类药物经常用于治疗晚期清细胞细胞癌 (ccRCC) 的疼痛.
- 已知长时间的阿片类药物暴露会影响血管系统,并具有免疫抑制性质.
- 长期使用阿片类药物对ccRCC代谢和生理学的影响仍未得到充分研究.
研究的目的:
- 调查长时间阿片类药物暴露对清细胞细胞癌的新陈代谢和免疫微环境的影响.
- 为了确定与阿片类药物使用相关的ccRCC瘤中的特定分子和细胞变化.
主要方法:
- 在存档的ccRCC样本上进行了RNA测序,这些样本来自有或没有长期阿片类药物暴露的患者.
- 使用CIBERSORT分析了免疫透和微环境变化.
- 进行了差异基因表达和KEGG通路分析.
主要成果:
- 暴露于阿片类药物的ccRCC瘤显示M1巨细胞和CD4记忆休息T细胞子集的显着减少.
- RNA测序揭示了基因表达特征从有氧糖解转向TCA循环,尼古丁酸代谢和cAMP信号通路的转变.
- 虽然一些免疫细胞变化是显著的,但其他变化没有达到统计学意义.
结论:
- 长时间的阿片类药物暴露显著改变了清细胞细胞癌的细胞代谢和免疫平衡.
- 这些ccRCC中的代谢和免疫变化可能会影响患者对瘤微环境或代谢向治疗的反应.
- 需要进一步的研究,以了解阿片类药物诱导的ccRCC变化的临床影响.
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