Prognostic value of intratumoral lymphocyte-to-monocyte ratio and M0 macrophage enrichment in tumor immune microenvironment of melanoma

Neil K Jairath; Mark W Farha; Ruple Jairath; Paul W Harms; Lam C Tsoi; Trilokraj Tejasvi

doi:10.2217/mmt-2020-0019

Prognostic value of intratumoral lymphocyte-to-monocyte ratio and M0 macrophage enrichment in tumor immune microenvironment of melanoma

Melanoma Manag. 2020 Nov 2;7(4):MMT51. doi: 10.2217/mmt-2020-0019.

Authors

Neil K Jairath¹, Mark W Farha¹, Ruple Jairath¹, Paul W Harms^{1

2}, Lam C Tsoi³, Trilokraj Tejasvi¹

Affiliations

¹ Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
² Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
³ Department of Computational Medicine & Bioinformatics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.

Abstract

Skin cutaneous melanoma is characterized by significant heterogeneity in its molecular, genomic and immunologic features. Whole transcriptome RNA sequencing data from The Cancer Genome Atlas of skin cutaneous melanoma (n = 328) was utilized. CIBERSORT was used to identify immune cell type composition, on which unsupervised hierarchical clustering was performed. Analysis of overall survival was performed using Kaplan-Meier estimates and multivariate Cox regression analyses. Membership in the lymphocyte:monocyte^low, monocyte^hi ^gh and M0^high cluster was an independently poor prognostic factor for survival (HR: 3.03; 95% CI: 1.12-8.20; p = 0.029) and correlated with decreased predicted response to immune checkpoint blockade. In conclusion, an M0-macrophage-enriched, lymphocyte-to-monocyte-ratio-low phenotype in the primary melanoma tumor site independently characterizes an aggressive phenotype that may differentially respond to treatment.

Keywords: RNA sequencing; cutaneous melanoma; immunotherapy; lymphocytes; macrophages; monocytes; tumor immune microenvironment.