乳酸诱导的TAMs代谢重编程通过C/EBPα-CD74轴损害了口腔状细胞癌中的抗原呈现能力
Mengyao Wang1,2,3, Mengqi Wang1,2,3, Zizhen Gong1,2,3
1Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Clinical and translational medicine
|March 10, 2026
概括
口腔瘤中的乳酸积累抑制了巨细胞中的CD74表达,损害了它们的抗瘤功能,促进了癌症的进展. 这突出了口腔状细胞癌 (OSCC) 免疫治疗的关键途径.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
背景情况:
- 在口腔状细胞癌 (OSCC) 中,瘤相关巨细胞 (TAM) 在疾病进展过程中失去抗瘤功能.
- 在OSCC中TAM功能障碍背后的确切机制仍然不清楚.
- CD74对抗原呈现至关重要,但其在TAM免疫功能中的特定作用尚未得到充分研究.
研究的目的:
- 阐明CD74在OSCC进展期间TAMs中的作用.
- 研究乳酸盐在瘤微环境 (TME) 中影响CD74表达和TAM功能的机制.
主要方法:
- 综合单细胞转录基因分析.
- 临床队列验证. 临床队列验证.
- CD74条件淘汰赛小鼠模型.
- 代谢分析和机理学研究.
主要成果:
- 在TME中的乳酸积累重编程TAM代谢,导致C/EBPα乙化和抑制CD74表达.
- 降低CD74的调节会损害TAM抗原呈现能力,并抑制T细胞激活.
- 在TAM中减少CD74表达与OSCC进展和较差的患者预后相关.
结论:
- 乳酸-C/EBPα-CD74轴在OSCC中关键调节TAM功能.
- 针对这一轴为OSCC免疫疗法提供了潜在的治疗策略.
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