Prognostic Value of the Intratumoral Lymphocyte to Monocyte Ratio and M0 Macrophage Enrichment in the Melanoma Immune Microenvironment

• DOI: 10.20944/preprints202009.0239.v1
• Publication Date: 2020-09-11T06:16:10Z
• Authors: Neil Jairath; Mark Farha; Ruple Jairath; Paul Harms; Lam Tsoi; Trilokraj Tejasvi
• Keywords: Immune checkpoint; Monocyte

Background: Cutaneous Melanoma (SKCM) is characterized by significant heterogeneity in its molecular, genomic, and immunologic characteristics. Methods: Whole transcriptome RNAseq data from The Cancer Genome Atlas of SKCM (n=328) was utilized. immune microenvironment using CIBERSORTX to identify cell type composition. Unsupervised hierarchical clustering performed based on content. Samples were separated into those obtained the primary tumor site regional skin or soft tissue (locoregional), distant metastasis lymph node (metastatic). Analysis overall survival (OS) Kaplan-Meier estimates Cox-regression multivariable analyses. Results: Four clusters identified, largely defined lymphocyte:monocyte (L:M) ratio, monocyte-enrichment, M0-macrophage-enrichment (L:MLow, MonocyteHigh, M0High; L:MLow, MonocyteMid, M0Low; L:MMid, MonocyteLow, L:MHigh, M0Low). M0High cluster demonstrated significantly worse OS than 2-4 locoregional group (HR 2.804, 95% CI 1.262–6.234, p=0.0114). Membership an independently poor prognostic factor for 3.03, 1.12–8.20, p=0.029). correlated with higher rates decreased predicted response checkpoint blockade compared other as determined Tumor Immune Dysfunction Exclusion tool (TIDE). Conclusion: Distinct a M0-macrophage-enriched, L:M ratio low phenotype melanoma characterize aggressive that may differentially respond treatment.