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Leptomeningeal disease (LMD) in melanoma patients is associated with significant neurological impairments and has a dismal outcome with a median survival of 1.8 months. Despite the therapeutic benefit of targeted therapies and immunotherapies for most kinds of Stage IV melanoma, patients with LMD do not typically benefit. A deeper understanding of the tumor microenvironment (TME) of LMD may provide more appropriate therapeutic selection. A retrospective analysis of subjects who underwent surgical resection with LMD (n=8) were profiled with seven color multiplex to evaluate the expression of the global immune suppressive hub - the signal transducer and activator of transcription 3 (STAT3) and for the presence of CD3 T cells, CD68+ monocytes, CD163 immune suppressive macrophages, CD11c+ antigen presenting cells (APCs) in association with the melanoma tumor marker S100B and DAPI for cellular nuclear identification. High-resolution cellular imaging and quantification was conducted using the Akoya Vectra Polaris. CD163+ macrophage is the most frequent immune cell population in the LMD TME. Occasional CD3+ T cells and CD11c+ APC are also identified, although the latter has concurrent expression of CD163. STAT3 nuclear localization is heterogeneously expressed in the various immune cell populations. Occasional immune cluster interactions can be seen in the tumor stroma and the tumor edge. In conclusion, the TME of LMD is largely devoid of CD3+ T cells, but is enriched for immune suppression and innate immunity.

neuro-oncology advances

LMD-20. Immune Suppressive Macrophages and Signal Transducer and Activator of Transcription 3 (STAT3) Expression are common in Melanoma Leptomeningeal Disease