LMD-16. Choroid plexus orchestrates anti-cancer immunity in leptomeninges

Abstract Choroid plexus (CP) forms an anatomically functional barrier between the blood and cerebrospinal fluid (CSF) that dictates the cellular and humoral composition of the CSF. The immunological response of CP to inflammatory stimuli, such as cancer, remains unclear. Here, we find that CP orchestrates the immune composition of CSF in the steady state as well as in the presence of metastatic cancer. We show that the circulation-derived leptomeningeal monocyte-macrophages entering the CSF through CP promote the growth of leptomeningeal metastasis (LM) by perturbing the environment with a storm of dozens of pro- and anti-inflammatory cytokines. Functional manipulation of Type II Interferon pathway specifically within inflamed leptomeninges revealed that IFN-γ can serve as a dominant signal, further recruiting peripheral myeloid cells and activating their protective anti-tumoral response. This preclinical strategy was sufficient to controll the growth of syngeneic LM cancer cells and delay the onset of lethal LM.