1456 Characterization of inter and intra tumor heterogeneity in primary melanoma and melanoma brain metastases

Abstract

Background Melanoma often metastasizes to the brain, 1 usu-ally with a lethal outcome. Recent studies have reported that systemic immunotherapies (IOT) are effective in patients (pts) with melanoma brain metastases (MBM). 2 3 Nevertheless, the failure of IOT in nearly half of patients with MBM leads to the urgency to deeper investigate mechanisms of intrinsic and acquired resistance. The aim of this study is to deeply charac-terize the tumor microenvironment (TME) of primary melanoma (PM) and MBM and to assess inter- and intra-tumor heterogeneity in order to identify potential strategies able to increase the success of IOT in pts with MBM. Formalin-fixed, paraffin-embedded (FFPE) tumor biopsies were derived from 7 PM and 14 MBM biopsies from different pts. was isolated from tumor regions and sub-jected to whole gene expression profiling (GEP). Ingenuity Pathway Analysis (IPA) was performed for enrichment assess-ment, and Microenvironment Cell Populations-counter (MCP-counter) method was used to estimate the abundance of immune and stromal infiltrated cell subpopulations. Selected transcripts including mRNA for CD163, CD45 and CD20 were evaluated by immunohistochemistry (IHC). Inter- and intra-tumor immune heterogeneity of n=59 selected immune protein was also determined in PM and MBM by digital spa-tial profiling (DSP) using Nanostring