CDKN1A和细胞衰老与晚期肺腺癌的免疫抵抗有关
Wang Shen1, Feidie Duan2, Shuiting Fu3
1Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Clinical and experimental medicine
|November 17, 2025
概括
晚期肺腺癌 (LUAD) 中高CDKN1A表达与免疫抑制瘤微环境相关,并预测免疫治疗的反应不佳. 这表明CDKN1A可能是克服治疗耐药性的目标.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 由CDKN1A标记的细胞衰老会影响瘤微环境 (TME) 中的癌症进展和炎症反应.
- 建议CDKN1A在耐药性中的作用,但其对晚期肺腺癌 (LUAD) 免疫疗法疗效的影响尚不清楚.
研究的目的:
- 在先进的LUAD中研究CDKN1A的生物特征.
- 分析其与途径调节,免疫透和免疫治疗反应的关联.
主要方法:
- 利用TCGA和SU2C-MARK队列来分析CDKN1A表达及其相关性.
- 采用单细胞RNA测序 (GSE148071) 来检查TME和细胞通信.
- 进行多变量考克斯回归以评估整体存活率 (OS) 和无进展存活率 (PFS).
主要成果:
- CDKN1A的表达与免疫抑制性TME正相关,包括癌症相关纤维细胞 (CAF) 和髓质衍生抑制细胞 (MDSC).
- 高CDKN1A与接受免疫疗法,但不接受化疗的患者的生存状况和PFS恶化有关,这表明其具有预测作用.
- 单细胞分析显示,CDKN1A与肌/内皮细胞相关的丰富,以及增强的TGFB信号传递 (SMAD3/4).
结论:
- CDKN1A的表达与细胞衰老和高级LUAD中的免疫抑制性TME有关.
- CDKN1A预测免疫治疗的耐药性,这表明它不仅仅是一个预后标记.
- 涉及老化或老态疗法的组合策略可能会在LUAD中克服免疫疗法耐药性.
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