RT-ICI therapy induces a distal immunometabolic axis that shapes systemic macrophage polarization and enhances local T cell immunity - PubMed
3 months ago
- #immunotherapy
- #colorectal cancer
- #macrophage polarization
- RT-ICI therapy induces a distal immunometabolic axis affecting systemic macrophage polarization and local T cell immunity.
- The study involved 18 patients with microsatellite-stable CRC liver metastases treated with high-dose RT followed by anti-PD-1 ICI.
- RT triggered an APOA2+ tumor cell state with enhanced lipid metabolism and increased circulating HDL.
- This metabolic shift activated CETP+ M2-like macrophages, which localized to non-irradiated tumor regions.
- Combination therapy expanded GZMB+ effector T cells and induced inflammatory-toxic T cells (IT_T) with high cytotoxicity.
- Irradiated tumor cells acted as 'in situ vaccines,' enhancing MHC-TCR interactions and promoting T cell differentiation.
- The findings suggest RT-ICI therapy enhances local immunity while modulating systemic lipid metabolism and macrophage polarization.