This paper details research into leptomeningeal metastasis (LM), a fatal complication of solid tumors in the central nervous system. The study uses multimodal analyses of human clinical specimens and immunocompetent mouse models of lung, breast, and melanoma cancers to investigate the immune response within the leptomeninges. Key findings indicate that the cytokine Interferon-gamma (IFNγ) is a critical mediator of anti-tumor activity in this anatomical space, and its presence correlates with improved patient survival. Mechanistically, T cells generate IFNγ, which acts on conventional dendritic cells (cDCs), supporting their maturation into CCR7+ DCs; these migratory DCs then produce cytokines like IL-12 and IL-15 to support the cytotoxic action of natural killer (NK) cells, ultimately controlling cancer cell growth independent of adaptive immunity and antigen presentation. This suggests a unique, innate immune-driven therapeutic strategy for treating tumors in this challenging area.
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