ReviewMedical oncology (Northwood, London, England)2026
Neuro-immune crosstalk in lung cancer brain metastasis: mechanisms, therapeutic targets, and translational opportunities.
Review in Medical oncology (Northwood, London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors.
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Abstract
Brain metastasis remains one of the most devastating complications of lung cancer, contributing to poor prognosis and limited therapeutic efficacy. Increasing evidence suggests that the development and progression of lung cancer brain metastasis are shaped by dynamic and reciprocal interactions among tumor cells, neural components, and immune elements within the brain microenvironment. Neurotrophic factors, neurotransmitters, and glial cells participate in blood-brain barrier remodeling, immune modulation, and metabolic adaptation, while tumor cells exploit these neuro-immune interactions to facilitate colonization, survival, and therapeutic resistance. In this review, we organize current knowledge within a stage-specific and spatiotemporal framework encompassing early blood-brain barrier disruption and colonization, intermediate microenvironmental remodeling with immunosuppression formation, and late-stage stabilization characterized by sustained neuro-tumor interaction. Importantly, rather than summarizing neural or immune pathways in isolation, we integrate adaptive immune dynamics, glial reprogramming, and neurotransmitter-dependent signaling into a unified neuro-immune-tumor network model and explicitly prioritize context-dependent hub molecules according to graded levels of supporting evidence. Within this staged framework, we delineate regulatory axes that may define context-dependent therapeutic windows. Rather than providing an exhaustive catalog of mechanisms, we emphasize pathways with emerging translational relevance, including BDNF-TrkB signaling, adrenergic pathways, and glial reprogramming. This integrative perspective aims to clarify the organizational principles of neuro-immune-tumor networks in lung cancer brain metastasis and to inform future studies exploring combinatorial neural and immune modulation strategies, biomarker development, and rational clinical trial design, while acknowledging that direct LCBM validation remains limited for some pathways.
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