Targeting SPP1 +TAMs associated with liver metastasis reverses immunosuppression and synergizes with immunotherapy in colorectal cancer - PubMed
5 hours ago
- #Tumor-Associated Macrophages
- #Colorectal Cancer
- #Immunotherapy
- Identified two distinct TAM populations: SPP1+ and SEPP1+ TAMs in colorectal cancer (CRC).
- SPP1+ TAMs are associated with angiogenesis, immune evasion, and liver metastasis, linked to poorer prognosis.
- SPP1+ TAMs have two metabolic subtypes: glycolytic ATP5F1E+ (primary tumors and lymph nodes) and oxidative phosphorylation-dominant MT-CO1+ (liver metastases).
- MT-CO1+ SPP1+ TAMs localize to oxygen-rich invasive margins, while ATP5F1E+ SPP1+ TAMs reside in hypoxic tumor cores.
- SPP1+ TAMs drive CD8+ T-cell exhaustion and spatial exclusion.
- Combined regorafenib and anti-PD-1 therapy reduced SPP1+ TAM infiltration and suppressed tumor growth and metastasis in preclinical models.
- Targeting SPP1+ TAMs presents a novel translational strategy for CRC immunotherapy.