Melanoma leptomeningeal disease: Advances in diagnosis and emerging therapeutic strategies

Figure 1 Pathophysiology of melanoma leptomeningeal disease. Created with BioRender.com. Melanoma cells disseminate from the primary tumor via hematogenous spread and traverse the central nervous system vascular-cerebrospinal fluid (CSF) interface to access the leptomeningeal space. Tumor cells spread diffusely along the pia and arachnoid mater within the CSF. The CSF microenvironment is marked by low immune surveillance, enriched transforming growth factor β signaling, scarce cytotoxic CD8+ T cells, abundant myeloid-derived suppressor cells, and exhausted CD4+ T cells, promoting tumor persistence and therapeutic resistance. CSF: Cerebrospinal fluid; CNS: Central nervous system; CTCs: Circulating tumor cells; MDSCs: Myeloid-derived suppressor cells; TGF: Transforming growth factor; ICIs: Immune checkpoint inhibitors.