The immune landscape of cerebrospinal fluid across brain malignancies

Abstract Cerebrospinal fluid (CSF) is an active immunological interface within the central nervous system, reflecting and shaping tumor–immune interactions that are often invisible in peripheral blood. Accumulating evidence demonstrates that CSF immune remodeling is highly malignancy-specific rather than uniform across brain cancers. In this review, we synthesize recent advances in CSF immune profiling across gliomas, primary CNS lymphomas, brain metastases, and leptomeningeal metastases, highlighting how each disease programs distinct cellular and cytokine circuits. Gliomas are characterized by myeloid skewing and IL-6–associated inflammation, CNS lymphomas by IL-10/CXCL13-driven B-cell–supportive niches, brain metastases by primary tumor–imprinted inflammatory signatures, and leptomeningeal metastases by profound macrophage dominance and complement-mediated immune reprogramming. Importantly, CSF alterations are not merely correlative but mechanistically linked to immune evasion, disease progression, and therapeutic responsiveness. We further discuss translational applications of CSF analysis for molecular stratification, immune monitoring, and treatment response assessment, and critically evaluate the emerging role of CSF-directed therapeutic strategies. Collectively, this review positions CSF as a biologically and clinically integrated compartment with growing relevance for precision neuro-oncology.