Single-cell RNA sequencing unveils the clonal and transcriptional landscape of cutaneous T-cell lymphomas
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ABSTRACT:
PROVIDER: PRJNA758074 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR15624154.fastq.gz | Fastqsanger.gz | |||
| SRR15624155.fastq.gz | Fastqsanger.gz | |||
| SRR15624156.fastq.gz | Fastqsanger.gz | |||
| SRR15624157.fastq.gz | Fastqsanger.gz |
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Project description:Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma, arising from clonal expansion of transformed skin-homing memory T cells. However, the lack of specific markers for malignant lymphocytes prevents distinguishing them from benign T cells in the tumor microenvironment (TME) of MF, thus delaying diagnosis and development of specific treatment, which results in poor clinical outcomes. Here we employed recent advances in single-cell RNA-sequencing to establish the transcriptome of expanded T-cell clones directly in advanced-stage MF skin tumors, allowing the transcriptional profiles of malignant and reactive T lymphocytes to be distinguished. Our analysis identified multiple non-overlapping expanded T-cell clonotypes within individual MF tumors, which included malignant and reactive clones. Heterogeneity among samples was observed not only in the number of expanded clonotypes but also in their TCR specificity and gene expression. While patient-specific tumorigenic pathways were up-regulated by the malignant clones, we also identified a common gene expression that included genes associated with cancer cell metabolism, de novo nucleotide biosynthesis, and invasion. Most non-malignant clones originated from CD8+ T cells and commonly presented an exhausted immune phenotype and activated Th1/Th2 pathways. While non-clonal infiltrating CD4+ and CD8+ lymphocytes from all tumors shared anti-inflammatory and immunosuppressive pathways, patient-specific mechanisms included the TNFR2 signaling cascade, ferroptosis, and cytotoxic pathways by gamma/delta T cells. Thus, scRNAseq reveals new insights in MF pathogenesis by providing an unprecedented report of the transcriptomes of malignant and reactive T cells in the TME of individual patients and offers novel prospective targets for personalized therapy.
2022-06-01 | GSE182861 | GEO
Project description:The oncogenic microRNA 17-92 cluster is involved in the lymphomagenesis of nodal and systemic B cell lymphomas, but has not been studied so far in primary cutaneous B cell lymphomas. We performed the quantitative analysis of miR-17-92 cluster and its paralogs miR-106a-363 and miR-106b-25 in 22 primary cutaneous diffuse large B-cell lymphomas-leg type (PCLBCL-LT) and 22 primary cutaneous follicle center lymphomas (PCFCL). Mir-20a and miR-106a were overexpressed in PCLBCL-LT compared to PCFCL. Multivariate Cox analysis showed that higher miR-20a and miR-20b were associated with poorer disease-free survival and poorer overall survival, independently of histological type. Gene expression profiling showed underexpression of 8 candidate target genes of miR-20a, miR-20b and miR-106a in PCLBCL-LT compared to PCFCL. Among the candidate target genes, PTEN, NCOA3 and CAPRIN2 were confirmed to be underexpressed in PCLBCL-LT using quantitative RT-PCR of laser-microdissected tumor cells. In multivariate Cox analysis, lower PTEN mRNA expression level was associated with poorer disease-free survival, independently of the histological type. Altogether, this molecular and bioinformatics study of patients’ skin biopsy samples showed that the oncogenic miR-17-92 cluster is involved in cutaneous B cell lymphoma progression, and that the down-regulation of its target gene PTEN is associated with poorer disease-free survival.
2016-12-31 | GSE55833 | GEO
Project description:PurposeClonal malignant T lymphocytes constitute only a fraction of T cells in mycosis fungoides skin tumors and in the leukemic blood of Sézary syndrome, the classic types of cutaneous T-cell lymphomas. However, lack of markers specific for malignant lymphocytes prevents distinguishing them from benign T cells, thus delaying diagnosis and the development of targeted treatments. Here we applied single-cell methods to assess the transcriptional profiles of both malignant T-cell clones and reactive T lymphocytes directly in mycosis fungoides/Sézary syndrome patient samples.Experimental designSingle-cell RNA sequencing was used to profile the T-cell immune repertoire simultaneously with gene expression in CD3+ lymphocytes from mycosis fungoides and healthy skin biopsies as well as from Sézary syndrome and control blood samples. Transcriptional data were validated in additional advanced-stage mycosis fungoides/Sézary syndrome skin and blood samples by immunofluorescence microscopy.ResultsSeveral nonoverlapping clonotypes are expanded in the skin and blood of individual advanced-stage mycosis fungoides/Sézary syndrome patient samples, including a dominant malignant clone as well as additional minor malignant and reactive clones. While we detected upregulation of patient-specific as well as mycosis fungoides- and Sézary syndrome-specific oncogenic pathways within individual malignant clones, we also detected upregulation of several common pathways that included genes associated with cancer cell metabolism, cell-cycle regulation, de novo nucleotide biosynthesis, and invasion.ConclusionsOur analysis unveils new insights into mycosis fungoides/Sézary syndrome pathogenesis by providing an unprecedented report of the transcriptional profile of malignant T-cell clones in the skin and blood of individual patients and offers novel prospective targets for personalized therapy.
| S-EPMC9197926 | biostudies-literature
Project description:Immunoglobulin gene rearrangement and somatic hypermutation have the potential to create neoantigens in non-Hodgkin B cell lymphoma. However, the presentation of these putative immunoglobulin neoantigens by B cell lymphomas has not been proven. We used MHC immunoprecipitation followed by liquid chromatography and tandem mass spectrometry (LC-MS/MS) to define antigens presented by follicular lymphomas (FL), chronic lymphocytic leukemias (CLL), diffuse large B cell lymphoma (DLBCL) and mantle cell lymphomas (MCL). We found presentation of the clonal immunoglobulin molecule, including neoantigens by both class I and class II MHC, though more commonly in class II MHC. To determine whether B cell activation could promote presentation of immunoglobulin neoantigens, we used a toll-like receptor 9 (TLR9) agonists to upregulate expression of MHC-II. This resulted in enhanced class II MHC presentation of the immunoglobulin variable region including neoantigens. These findings demonstrate that immunoglobulin neoantigens are presented across most subtypes of B cell lymphomas. Activation of lymphoma cells to upregulate antigen presentation boosts presentation of immunoglobulin neoantigens and represents a strategy for augmenting lymphoma immunotherapies.
2019-01-07 | PXD010808 | Pride
Project description:We studied gene expression profiles of 17 cutaneous B-cell lymphomas that were collected with 4-6 millimeter skin punch biopsies. We also included tissue from 2 cases of mycosis fungoides (MF), 3 normal skin biopsies and 3 tonsils to create a framework for further interpretation. A hierarchical cluster algorithm was applied for data analysis. Our results indicate that small amounts of skin tissue can be used successfully to perform microarray analysis and result in distinct gene expression patterns. Duplicate specimens clustered together demonstrating a reproducible technique. Within the cutaneous B-cell lymphoma specimens two specific B-cell differentiation stage signatures of germinal center B-cells and plasma cells could be identified. Primary cutaneous follicular and primary cutaneous diffuse large B-cell lymphomas had a germinal center B-cell signature while a subset of marginal zone lymphomas demonstrated a plasma cell signature. Primary and secondary follicular B-cell lymphoma of the skin were closely related, despite previously reported genetic and phenotypic differences. In contrast primary and secondary cutaneous diffuse large B-cell lymphoma were less related to each other. This pilot study allows a first glance into the complex and unique microenvironment of B-cell lymphomas of the skin and provides a basis for future studies, that may lead to the identification of potential histologic and prognostic markers as well as therapeutic targets. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed
2005-12-16 | E-GEOD-3827 | biostudies-arrayexpress
Project description:Cutaneous T-cell lymphomas are a heterogeneous group of neoplasms originating in the skin, with mycosis fungoides (MF) and Sézary syndrome (SS) representing the most common variants. The cellular origin of cutaneous lymphomas has remained controversial due to their immense phenotypic heterogeneity that obfuscates lineage reconstruction based on classical surface biomarkers. To overcome this heterogeneity and reconstruct the differentiation trajectory of malignant cells in MF and SS, T-cell receptor sequencing was performed in parallel with targeted transcriptomics at the single-cell resolution among cutaneous samples in MF and SS. Unsupervised lineage reconstruction showed that Sézary cells exist as a population of CD4+ T cells distinct from those in patch, plaque, and tumor MF. Further investigation of malignant cell heterogeneity in SS showed that Sézary cells phenotypically comprised at least three subsets based on differential proliferation potentials and expression of exhaustion markers. A Th1 polarized cell type, intermediate cell type, and exhausted Th2 polarized cell type were identified, with Th1 and Th2 polarized cells displaying divergent proliferation potentials. Collectively, these findings provide evidence to clarify the relationship between MF and SS, and reveal cell subsets in SS that suggest a possible mechanism for therapeutic resistance.
2022-12-31 | GSE192836 | GEO
Project description:We studied gene expression profiles of 17 cutaneous B-cell lymphomas that were collected with 4-6 millimeter skin punch biopsies. We also included tissue from 2 cases of mycosis fungoides (MF), 3 normal skin biopsies and 3 tonsils to create a framework for further interpretation. A hierarchical cluster algorithm was applied for data analysis. Our results indicate that small amounts of skin tissue can be used successfully to perform microarray analysis and result in distinct gene expression patterns. Duplicate specimens clustered together demonstrating a reproducible technique. Within the cutaneous B-cell lymphoma specimens two specific B-cell differentiation stage signatures of germinal center B-cells and plasma cells could be identified. Primary cutaneous follicular and primary cutaneous diffuse large B-cell lymphomas had a germinal center B-cell signature while a subset of marginal zone lymphomas demonstrated a plasma cell signature. Primary and secondary follicular B-cell lymphoma of the skin were closely related, despite previously reported genetic and phenotypic differences. In contrast primary and secondary cutaneous diffuse large B-cell lymphoma were less related to each other. This pilot study allows a first glance into the complex and unique microenvironment of B-cell lymphomas of the skin and provides a basis for future studies, that may lead to the identification of potential histologic and prognostic markers as well as therapeutic targets. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
2005-12-17 | GSE3827 | GEO
Project description:Addiction of primary cutaneous gamma-delta T-cell lymphomas to JAK-STAT signaling
| PRJNA1184839 | ENA
Project description:Addiction of primary cutaneous gamma-delta T-cell lymphomas to JAK-STAT signaling
| PRJNA1184840 | ENA
Project description:High-throughput sequencing of primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) and in vitro activated peripheral blood B-cells. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Lymphoma miRNA profiles of were generated by deep sequencing, using Illumina Genome Analyzer II.
2013-10-18 | E-GEOD-51359 | biostudies-arrayexpress