TMIC-02. PRE-SURGICAL IMMUNE CHECKPOINT BLOCKADE RESHAPES THE IMMUNE LANDSCAPE AND SPATIAL ARCHITECTURE OF METASTATIC BRAIN TUMORS

Abstract Brain tumors reside in a modified microenvironment where inflammatory processes are heavily regulated. Nevertheless, our recent study showed significant immune infiltration recurrent glioblastoma (rGBM) treated with neoadjuvant PD-1 checkpoint blockade therapy. In comparison to GBM, the intracranial response of brain metastases (BrM) immunotherapy has been less well studied. To test this question, we investigated effect pre-surgical (ICB) on compartments BrM, using multiplex immunofluorescence, single-cell RNA sequencing and spatial transcriptomics total 17 patients. We found that ICB naïve BrM featured an exclusion phenotype accumulation cells fibrovascular stroma, necrotic hemorrhagic peritumoral areas. Following treatment, T monocyte-derived macrophages were then observed within tumor parenchyma. Computational receptor-ligand analysis suggested tumor-infiltrating highly engaged by pairing, which may drive into advanced exhausted state. further explore organization interactions between immune, stroma utilized sequencing-based technology. Our data highlighted distinct architectures –treated tumors. It also pinpointed unique macrophage subset preferentially co-localized vasculature confined infiltrates perivascular space. summary, revealed ICB-induced marked changes composition offers insights new combination therapies can help improve clinical efficacy for