瘤衍生殖民地刺激因子1 (CSF1) 的阻塞促进了免疫允许性瘤微环境
Maria Del Mar Maldonado1, Jeffrey Schlom2, Duane H Hamilton1
1Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Cancer immunology, immunotherapy : CII
|July 28, 2023
概括
通过阻断抗体向巨菌群刺激因子1受体 (CSF1R),可以增强抗瘤免疫力. 将CSF1R抑制与疫苗或抗PDL1治疗相结合,有望减少瘤生长和转移.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 大细胞殖民地刺激因子1 (CSF1) 对于单核细胞发育至关重要.
- CSF1/CSF1受体 (CSF1R) 轴在瘤中经常过度表达,促进侵入性和转移.
- 由CSF1招募的瘤相关巨细胞 (TAMs) 可以创建一个免疫抑制的微环境.
研究的目的:
- 在已建立的小鼠结肠癌和乳腺癌模型中研究CSF1R阻断抗体的治疗潜力.
- 评估抑制瘤衍生的CSF1对瘤生长和抗瘤免疫力的影响.
- 评估涉及用疫苗或免疫检查点抑制剂抑制CSF1R的组合疗法.
主要方法:
- 在瘤细胞中生成和表征CSF1 CRISPR-Cas9淘汰.
- 用阻断CSF1R的抗体治疗已建立的突发性小鼠瘤.
- 使用抗CSF1R与新表位疫苗或抗PDL1.1的组合疗法研究.
- 对瘤微环境的分析,包括免疫细胞透 (CD8 T细胞) 和TAMs.
主要成果:
- 抑制CSF1R促进了新表位特异性T细胞的扩张.
- 消除瘤衍生的CSF1降低了瘤生长和增强了抗neoepitope免疫力.
- 与adeno-TWIST1疫苗结合抗CSF1R疗法控制了4T1乳腺瘤的瘤生长和减少了转移.
- 结合新表皮疫苗与抗PDL1的结合显著降低了MC38 CSF1-/-瘤的瘤生长.
- 抑制CSF1R导致CD8 T细胞透率增加和TAMs减少.
结论:
- 针对CSF1R轴可以重新编程瘤微环境以增强抗瘤免疫力.
- 涉及用疫苗或免疫检查点封锁抑制CSF1R的组合策略具有显著的治疗潜力.
- 这些发现支持通过调节抗neoepitope反应来开发用于癌症免疫治疗的CSF1向剂.
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