Characterization of the cutaneous tumor microenvironment of advanced-stage mycosis fungoides using single-cell RNA sequencing

Malignant T lymphocyte proliferation in mycosis fungoides (MF) is largely restricted to the skin, implying that malignant cells are dependent on their specific cutaneous tumor microenvironment (TME), including interactions with non-malignant immune and stromal cells, cytokines, and other immunomodulatory factors. To explore these interactions, we performed a comprehensive transcriptome analysis of the TME in advanced-stage MF skin tumors by single-cell RNA sequencing. Our analysis identified cell-type compositions, cellular functions, and cell-cell interactions in the MF TME that were distinct from those from healthy skin and benign dermatoses. While patterns of gene expression were common amongst patient samples, high transcriptional diversity was also observed in immune and stromal cells, with dynamic interactions and crosstalk between these cells and malignant T lymphocytes. This heterogeneity mapped to processes such as cell trafficking, matrix interactions, angiogenesis, immune functions, and metabolism that affect cancer cell growth, migration and invasion, as well as anti-tumor immunity. By comprehensively characterizing the transcriptomes of immune and stromal cell within the cutaneous microenvironment of individual MF tumors, we have identified patterns of dysfunction common to all tumors that represents a resource for identifying candidates with therapeutic potential as well as patient-specific heterogeneity that has important implications for personalized disease management. 7 CTCL samples and 9 normal skin samples were analyzed. MF17,MF18,MF21, and MF21 were reused from GSE182861.