由乳酸分化的SPP1+巨细胞赋予大脑中缺氧适应性瘤细胞的进展
Jianlei Zhang1,2, Zhihui Li1,3, Jiang Yin1
1Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, Guangdong, 510095, China.
Neuro-oncology
|September 19, 2025
概括
大脑瘤细胞通过HIF-1信号来适应缺氧,招募巨细胞. 针对SPP1+巨细胞和乳酸代谢提供了新的脑瘤治疗策略,增强了免疫疗法.
科学领域:
- 神经瘤学神经瘤学
- 癌症免疫学 癌症免疫学
- 瘤微环境研究研究
背景情况:
- 大脑恶性瘤,包括原发性瘤和转移,在很大程度上是无法治愈的.
- 驱动脑瘤进展和抵抗的潜在机制尚未完全理解.
- 对泛大脑瘤微环境的全面调查对于治疗开发至关重要.
研究的目的:
- 为了研究泛大脑瘤微环境.
- 为了阐明脑瘤中缺氧适应能力的机制.
- 确定改善脑瘤治疗结果的治疗点.
主要方法:
- 用转基因小鼠和立体注射用于脑瘤模型.
- 采用单细胞RNA测序和空间转录组学来进行全面的分析.
- 应用CRISPR/Cas9基因编辑,流细胞计和分子测试来验证发现.
主要成果:
- 鉴定了脑瘤中增强的缺氧诱导因子1 (HIF-1) 信号传递,从而赋予了生长优势.
- 揭示了瘤低氧适应能力和巨细胞透之间的相互依赖.
- 证明分泌的蛋白1 (SPP1) +巨细胞促进瘤生长并抑制CD8 + T细胞活性,同时向LDHA与抗PD-1疗法进行协同作用.
结论:
- 缺氧瘤细胞和巨细胞之间的相互作用是脑瘤微环境的关键特征.
- SPP1+巨体代表了重塑脑瘤微环境的潜在治疗标.
- 向乳酸代谢和SPP1+巨细胞可能会提高抗PD-1等免疫疗法的疗效.
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