Single cell rna sequencing reveals differential dendritic cell subtypes in early vs. late-stage mycosis fungoides disease

Summary: Abstract Body: In the tumor microenvironment of mycosis fungoides (MF), dendritic cells (DC) play a dual role in promoting and restraining disease progression; however, DC subtypes in MF disease are not well-defined. Immature DCs expressing DC-SIGN/CD209 have been shown to be highly expressed in late-stage MF and are associated with T-cell tolerance. To identify DC subtypes, single-cell RNA sequencing techniques were applied to dissociated skin tissue from one unaffected patient, two early-stage, and two late-stage MF patients. 1138 dendritic cells were identified using canonical gene markers. Analysis of the top 3000 most highly variable expressed genes revealed four DC subclusters. The top 5 DEGS per subcluster and gene ontology analysis identified clusters 0, 1, and 3 as conventional DCs (cDC) and cluster 2 as plasmacytoid DCs. Cluster 0 was identified as a mature, partially activated cDC population (CD14+/CD83mid) and was decreased in all MF patients compared to the control sample. Cluster 1 was identified as an immature, inactivated cDC population (CD14+/CD83low) and was increased in early-stage MF patients. Cluster 3 was identified as mature/fully activated cDCs (CD14+/CD83high) and was more prominent in MF patients than in the control group, with an increased number in early-stage MF. Interestingly, Cluster 3 had significant gene expression of DC-SIGN/CD209 (log2FC = 2.1, p = 2.16E-18), suggesting this mature DC cluster may be responsible for MF disease progression. Further defining DC subtypes by MF stage will provide new insights into disease progression. Daniela Barata Herrera¹, Weishaun Li⁴, Soroosh Solhjoo³, Iman Ali¹, Kalvin Nash¹, Stephanie Hicks⁴, Winston Timp², Courtney Johnson¹ 1. Dermatology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States. 2. Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States. 3. Medicine, Uniformed Services University of the Health Sciences F Edward Hebert School of Medicine, Bethesda, MD, United States. 4. Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States. Translational Studies: Cell and Molecular Biology