The immune microenvironment of the central nervous system and neuromodulation: new perspectives in lung cancer brain metastases research

Brain metastases (BM) from lung cancer remain a devastating complication that severely compromises patient survival. Its development is driven by dynamic and complex interactions between tumor cells and the central nervous system microenvironment, involving blood-brain barrier disruption, immunosuppressive niche formation, neural co-optation, metabolic adaptation, and peripheral immune dysregulation. Current strategies face intrinsic resistance and delivery barriers. This review aimed to systematically examine these mechanisms and therapeutic frontiers, including emerging interventions that preserve vascular-neural integrity, intercept neurotransmitter-mediated tumor support, reprogram brain resident cells, exploit metabolic vulnerabilities, and engineer advanced delivery systems, thereby proposing directions to overcome therapeutic challenges in lung cancer BM.