Version 1
: Received: 9 September 2020 / Approved: 11 September 2020 / Online: 11 September 2020 (04:02:03 CEST)
How to cite:
Jairath, N.; Farha, M.; Jairath, R.; Harms, P.; Tsoi, L.; Tejasvi, T. Prognostic Value of the Intratumoral Lymphocyte to Monocyte Ratio and M0 Macrophage Enrichment in the Melanoma Immune Microenvironment. Preprints2020, 2020090239. https://doi.org/10.20944/preprints202009.0239.v1
Jairath, N.; Farha, M.; Jairath, R.; Harms, P.; Tsoi, L.; Tejasvi, T. Prognostic Value of the Intratumoral Lymphocyte to Monocyte Ratio and M0 Macrophage Enrichment in the Melanoma Immune Microenvironment. Preprints 2020, 2020090239. https://doi.org/10.20944/preprints202009.0239.v1
Jairath, N.; Farha, M.; Jairath, R.; Harms, P.; Tsoi, L.; Tejasvi, T. Prognostic Value of the Intratumoral Lymphocyte to Monocyte Ratio and M0 Macrophage Enrichment in the Melanoma Immune Microenvironment. Preprints2020, 2020090239. https://doi.org/10.20944/preprints202009.0239.v1
APA Style
Jairath, N., Farha, M., Jairath, R., Harms, P., Tsoi, L., & Tejasvi, T. (2020). Prognostic Value of the Intratumoral Lymphocyte to Monocyte Ratio and M0 Macrophage Enrichment in the Melanoma Immune Microenvironment. Preprints. https://doi.org/10.20944/preprints202009.0239.v1
Chicago/Turabian Style
Jairath, N., Lam Tsoi and Trilokraj Tejasvi. 2020 "Prognostic Value of the Intratumoral Lymphocyte to Monocyte Ratio and M0 Macrophage Enrichment in the Melanoma Immune Microenvironment" Preprints. https://doi.org/10.20944/preprints202009.0239.v1
Abstract
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. The immune microenvironment was characterized using CIBERSORTX to identify immune cell type composition. Unsupervised hierarchical clustering was performed based on immune cell type content. Samples were separated into those obtained from the primary tumor site and regional skin or soft tissue (locoregional), or distant metastasis and regional lymph node (metastatic). Analysis of overall survival (OS) was performed using Kaplan-Meier estimates and Cox-regression multivariable analyses. Results: Four immune clusters were identified, largely defined by lymphocyte:monocyte (L:M) ratio, monocyte-enrichment, and M0-macrophage-enrichment (L:MLow, MonocyteHigh, M0High; L:MLow, MonocyteMid, M0Low; L:MMid, MonocyteLow, M0Low; L:MHigh, MonocyteLow, M0Low). The L:MLow, MonocyteHigh, M0High cluster demonstrated significantly worse OS than clusters 2-4 in the locoregional group (HR 2.804, 95% CI 1.262–6.234, p=0.0114). Membership in the L:MLow, MonocyteHigh, M0High cluster was an independently poor prognostic factor for survival (HR 3.03, 95% CI 1.12–8.20, p=0.029). The L:MLow, MonocyteHigh, M0High cluster correlated with higher rates of metastasis and decreased predicted response to immune checkpoint blockade compared to the other clusters as determined by the Tumor Immune Dysfunction and Exclusion tool (TIDE). Conclusion: Distinct tumor immune clusters with a M0-macrophage-enriched, L:M ratio low phenotype in the primary melanoma tumor site independently characterize an aggressive phenotype that may differentially respond to treatment.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
