Study the interactions between alveolar macrophages and T cells in non-small cell lung cancer

Division Of Basic Sciences - Nci

Investigators

Abstract

Building on the innovative dual-marker Cre recombinase mouse model developed last year to specifically target alveolar macrophages (AMs), we have now employed the uLIPSTIC system by crossing uLIPSTIC mice with our SiglecF/CD11c-specific Cre line. This approach enables high-resolution tracking of immune cell interactions with AMs in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). Using this system, we have identified regulatory T cells (Tregs), particularly Th1-like Tregs, as the predominant immune cell population interacting with AMs in the TME. This finding suggests a potential role for AMs in influencing the phenotypic plasticity between conventional Tregs and Th1-like Tregs-either promoting conversion from one subset to the other or maintaining a dynamic balance between the two. To directly investigate this hypothesis, we have developed a novel Treg lineage tracing model, which will allow us to monitor the fate and functional transitions of Tregs in the presence or absence of AMs. This tool will help elucidate the molecular mechanisms governing AM-Treg interactions and their impact on immune modulation in lung cancer, potentially revealing new therapeutic targets for enhancing anti-tumor immunity.