Tumour microenvironment heterogeneity in primary and metastatic paired melanoma samples and its correlation with genetic features and prognosis.

BackgroundThe prognostic impact of tumour microenvironment (TME) heterogeneity in primary cutaneous melanomas (CM) and paired distant metastases is unclear. Few studies have explored the impact of genetic features on TME immune cell distribution. This study assessed the prognostic impact of TME heterogeneity and investigated the correlation between genetic features and TME cell composition.MethodsDemographics, treatments and outcome of melanoma patients - with paired samples - from five Italian Melanoma Intergroup (IMI) centers were collected. TME immune phenotypes and cell distribution in FFPE whole tumour sections were analyzed using 9 biomarkers (CD3, CD4, CD8, CD20, CD68, CD163, PD-1, PD-L1, FOXP3), classifying samples as desert (D), excluded (E), or inflamed (I). Additionally, genomic pathways were assessed by next-generation sequencing in both primary and paired samples.ResultsTME was evaluated in 221 samples from 91 patients.The distribution of immune phenotype (I vs E/D) of CD8 + cells (p