Targeting SPP1 +TAMs associated with liver metastasis reverses immunosuppression and synergizes with immunotherapy in colorectal cancer - PubMed
2 months ago
- #Tumor-Associated Macrophages
- #Colorectal Cancer
- #Immunotherapy
- 在结直肠癌(CRC)中发现两种独特的肿瘤相关巨噬细胞(TAM)亚群：SPP1+和SEPP1+ TAM
- SPP1+ TAM与血管生成、免疫逃逸和肝转移相关，提示患者预后较差
- SPP1+ TAM存在两种代谢亚型：糖酵解主导的ATP5F1E+型(原发灶和淋巴结)与氧化磷酸化主导的MT-CO1+型(肝转移灶)
- MT-CO1+ SPP1+ TAM富集于富氧的肿瘤侵袭前沿，而ATP5F1E+ SPP1+ TAM分布于缺氧的肿瘤核心区
- SPP1+ TAM会驱动CD8+ T细胞耗竭并导致其空间排斥
- 临床前模型显示，瑞戈非尼联合PD-1抑制剂可减少SPP1+ TAM浸润并抑制肿瘤生长转移
- 靶向SPP1+ TAM为结直肠癌免疫治疗提供了新的转化策略