Single-cell RNA sequencing reveals tissue compartment-specific plasticity of mycosis fungoides tumor cells
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ABSTRACT:
PROVIDER: PRJNA695230 | ENA |
REPOSITORIES: ENA
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Project description: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.
2021-04-13 | GSE165623 | GEO
Project description:Mycosis fungoides (MF) is the most common and best studied of cutaneous T-cell lymphoma (CTCL). Three clinical cutaneous stages have been described (patch, plaque and tumor) as the disease progress developing also the disease lymph node, peripheral blood or systemic involvement in late stages. Clinical and pathologic diagnosis of early MF stages (patch and plaque) is difficult as its morphologic similarity to inflammatory dermatoses and low proportion of tumoral cells.
2018-06-21 | GSE109421 | GEO
Project description:Mycosis fungoides patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present EORTC multicenter study, the genomic profile of 41 skin biopsies from tumor-stage mycosis fungoides was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2 and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21 and 10q26qter were defined as prognostic markers exhibiting a significant correlation with overall survival (P= .042, P= .017 and P= .022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (> 5 DNA aberrations), showing that the genomic unstable group had a shorter overall survival (P=.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B and MTAP), and 10q26qter (MGMT and EBF3) may play an important role in prognosis. In addition, we describe the MFt genomic instability profile. Forty-one MFt were studied by arrayCGH using the Human Genome CGH 44K microarrays (G4410B and G4426B, Agilent Technologies, Palo Alto, CA, USA). In each microarray experiment, DNA obtained from a 20x10 um sections snap frozen samples from tumoral MF lesions was compared with commercial pools of healthy female DNA (Promega, Madison, WI, USA).
2010-05-06 | E-GEOD-18098 | biostudies-arrayexpress
Project description:Mycosis fungoides patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present EORTC multicenter study, the genomic profile of 41 skin biopsies from tumor-stage mycosis fungoides was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2 and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21 and 10q26qter were defined as prognostic markers exhibiting a significant correlation with overall survival (P= .042, P= .017 and P= .022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (> 5 DNA aberrations), showing that the genomic unstable group had a shorter overall survival (P=.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B and MTAP), and 10q26qter (MGMT and EBF3) may play an important role in prognosis. In addition, we describe the MFt genomic instability profile.
2009-09-15 | GSE18098 | GEO
Project description:We performed transcriptome analysis and multimodal data integration of the transcriptome and the microbiome of the skin of Mycosis fungoides Patients.
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Project description:We identified skin microbiota signatures related to different symptoms, i.e. pain, pruritus, in patients with Mycosis Fungoides.
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Project description:We used targeted single cell RNA sequencing using a gene set composed of the BD Rhapsody Human Immune Response Panel, TCR panel, and a custom panel of 61 malignancy-associated genes and T/B cell receptor sequencing to characterize single cell populations in hypopigmented mycosis fungoides (HMF). Using a reference mapping model built on publically deposited classic mycosis fungoides single cell RNA sequencing datasets, we identified a predicted malignant cell population independent from the clonal T cell population in HMF.
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Project description:NanoString based gene expression data from skin biopsies from nine mycosis fungoides patients before and after phototherapy as well as four healthy donor skin as a comparator
2023-06-14 | GSE234854 | GEO
Project description:NanoString based gene expression data from skin biopsies from nine mycosis fungoides patients before and after phototherapy as well as four healthy donor skin as a comparator
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