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Single-cell RNA sequencing reveals tissue compartment-specific plasticity of mycosis fungoides tumor cells

UID: 10616

Author(s): Rindler, Katharina, Bauer, Wolfgang, Jonak, Constanze, Wielscher, Matthais, Shaw, Lisa E, Rojahn, Thomas B., Thaler, Felix M., Porkert, Stefanie, Simonitsch-Klupp, Ingrid, Weninger, Wolfgang, Mayerhoefer, Marius E*, Farlik, Matthias, Brunner, Patrick M * MSK affiliated

Description
Summary from the GEO: "Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. While initially restricted to the skin, malignant cells can appear in blood, bone marrow and secondary lymphoid organs in later disease stages. However, only little is known about phenotypic and functional properties of malignant T cells in relationship to tissue environments over the course of disease progression. We thus profiled the tumor micromilieu in skin, blood and lymph node in a patient with advanced MF using single-cell RNA sequencing combined with V-D-J T-cell receptor sequencing. In skin, we identified clonally expanded T-cells with characteristic features of tissue-resident memory T-cells (TRM, CD69+CD27-NR4A1+RGS1+AHR+). In blood and lymph node, the malignant clones displayed a transcriptional program reminiscent of a more central memory-like phenotype (KLF2+TCF7+S1PR1+SELL+CCR7+), while retaining tissuehoming receptors (CLA, CCR10). The skin tumor microenvironment contained potentially tumor-permissive myeloid cells producing regulatory (IDO1) and Th2-associated mediators (CCL13, CCL17, CCL22). Given their expression of PVR, TNFRSF14 and CD80/CD86, they might be under direct control by TIGIT+CTLA4+CSF2+TNFSF14+ tumor cells. In sum, this study highlights the adaptive phenotypic and functional plasticity of MF tumor cell clones. Thus, the TRM-like phenotype enables long-term skin residence of MF cells. Their switch to a TCM-like phenotype with persistent skin homing molecule expression in the circulation might explain the multi-focal nature of MF."

Overall design: "multi-organ single-cell RNA-seq investigation of a primary cutaneous lymphoma"
Subject of Study
Homo sapiens
Subject(s)
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Mycosis Fungoides
OncoTree Cancer Type(s)
Mature T and NK Neoplasms
Mycosis Fungoides
Access via GEO

CSV, MTX, TSV files of expression profiling by high throughput sequencing
Accession #: GSE165623

Access via BioProject

Additional information about overall initiative
Accession #: PRJNA695230

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications
Rindler K, Bauer W, Jonak C, et al. Single-cell RNA sequencing reveals tissue compartment-specific plasticity of mycosis fungoides tumor cells. Frontiers in Immunology. 2021; 12:666935.
Data Type
Genomic
Equipment Used
Illumina NovaSeq 6000
Dataset Format(s)
CSV, TSV, TAR, MTX
Data Tool(s)
RNA Seq
Dataset Size
62.4 MB (TAR)
Data Catalog Record Updated
2021-11-04