Lipid metabolic reprogramming of macrophage by host APOBEC3 deficiency enhances anti-tumor immunity
Menée à l'aide de modèles murins génétiquement modifiés, cette étude démontre que la déficience de la désaminase de cytidine APOBEC3 améliore l'immunité antitumorale en modifiant le métabolisme lipidique des macrophages
Background : Tumour-associated macrophages are an indispensable part of the tumour immune microenvironment, exhibiting phenotypic and functional plasticity that enables them to play an important role in modulating the immune response. A large number of RNA editing events have been identified during macrophage functional remodelling. APOBEC3 is a well-known family of base-editing enzymes, but whether and how it regulates macrophage function is unclear.
Methods : In this study, we mainly used genetically engineered mice to demonstrate how host APOBEC3 deficiency affects tumour progression.
Results : We found that the polarisation state of macrophages in the tumour microenvironment was altered by host APOBEC3 deficiency and that knockout of host APOBEC3 significantly inhibited tumour growth and metastasis in a macrophage-dependent manner. Moreover, APOBEC3 deficiency remodelled macrophage function, improved their polarisation state, and enhanced their phagocytic capacity. Mechanistically, APOBEC3 knockout attenuated lipid uptake by macrophages in a PPAR
γ pathway-dependent way, leading to an increase of M1/M2 ratio in macrophages.
Conclusions
:
These findings reveal that APOBEC3 deficiency drives lipid metabolism reprogramming in macrophages and remodels their functions, thereby inducing a strong anti-tumour immune response, providing a proof-of-concept and new insights for the development of the APOBEC3 family for novel tumour therapies.
British Journal of Cancer , article en libre accès, 2026