Elucidating the interplay between Treg cells and novel macrophage subsets in the tumor microenvironment as a potential strategy for combination cancer immunotherapy 2908

Abstract Description Abstract Immunosuppressive tumor microenvironment limits the effectiveness of current cancer immunotherapies. T regulatory (Treg) cells maintain immune homeostasis and suppress anti-tumor immunity. Intratumoral Tregs express CCR8 and correlate with poor prognosis. While systemic Treg depletion in tumor-bearing mice restricts tumor growth it also induces compensatory changes in TME cell populations, particularly in macrophage subsets. These changes may counteract the anti-tumor effects, highlighting the need to understand the complex crosstalk between Tregs and macrophages. Our study investigates Treg-macrophage interactions by analyzing how Tregs influence macrophage subsets in tumor progression. Using bone marrow-derived macrophages co-cultured with Tregs, we identify signaling pathways and molecular interactions. We investigated macrophages in the presence and absence of Tregs. Without Tregs, macrophages exhibit altered gene expression to maintain immunosuppression. Using a tumor slice culture model, we study these interactions within an intact TME and evaluate targeted interventions. Our findings will guide in vivo studies in a non-small cell lung cancer model, combining CCR8-targeted Treg depletion with macrophage-modulating therapies. By elucidating Treg-macrophage crosstalk, we aim to identify novel therapeutic targets to disrupt TME-driven immune suppression and enhance combination immunotherapy for solid tumors. Funding Sources Supported by Dalia Greindinger anti Cancer fund Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)