Morpho-phenotypic characterization of melanoma brain metastases immune microenvironment: A multicentre retrospective study

The recent rise of immunotherapy for melanoma brain metastases (MBM) has enhanced the interest in characterizing the composition of local immune microenvironment. Despite the central nervous system (CNS) is well known for harbouring a peculiar immunological milieu, its role in MBM is only partially understood. The aim of our study was to characterize tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) distribution and density in a cohort of MBM and their potential relevance as prognostic biomarkers. Ninety-four MBM patients were retrospectively evaluated for morphological, molecular features and follow-up data. Formalin-fixed and paraffin-embedded (FFPE) tissue sections were immunostained with the following antibodies: CD4, CD8, FoxP3 CD68, CD163, PD-L1, HLA-ABC. Semiquantitative assessment of TILs and TAMs density and spatial distribution was performed and statistical analysis for prognostic correlations was carried out. The distribution of CD4+ TILs was higher in the intratumoral region (p=0.012) while CD163+ TAMs in the peritumoral (p=0.016). An association was also found between tumour-associated astrogliosis (TAA) and CD163+ TAMs (p=0.021). Increased CD68+ TAMs correlated with BRAF V600 mutation (p=0.038). CD4+ TILs were significantly higher in PD-L1