F330ce19-a47a-4029-9493-4558840c0bdd - samples
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ABSTRACT:
PROVIDER: EGAD00001009818 | EGA |
REPOSITORIES: EGA
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Project description:Hodgkin-like adult T-cell leukemia/lymphoma (ATLL) is a rare subtype of ATLL harboring human T cell lymphotropic virus type-1-infected Hodgkin-Reed-Sternberg (HRS)-like cells and small to medium CD4+ T cells, which histologically mimics classic Hodgkin lymphoma (CHL). CD30+ tumor cells or HRS cells are surrounded by CD4+ non-neoplastic T cells in a rosette-like manner in CHL. Interaction between HRS cells and surrounding CD4+ T cells is important for tumor microenvironment (TME) in CHL. Tumor microenvironment of Hodgkin-like ATLL remains unclear. Here, Digital Spatial Profiling was performed on Hodgkin-like ATLL to elucidate the interaction between HRS-like cells and CD4+ T cells in Hodgkin-like ATLL. We identified CD4+ T cells expressing co-stimulatory molecules, CD28 and inducible T cell co-stimulator (ICOS), in CD4+ T cells surrounding the HRS-like cells than in those apart from HRS-like cells. Immunohistochemistry was performed in 11 cases of Hodgkin-like ATLL, which detected distinct CD4+ T cells expressing CD28 in a rosette-like manner around HRS-like cells. HRS-like cells widely expressed CD80 and CD86, which suggested CD28-CD80/CD86 interaction was important in pathogenesis of Hodgkin-like ATLL. ICOS and immune checkpoint molecules, including T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and programmed death-1 (PD-1) were also variably expressed in CD4+ T cells surrounding HRS-like cells. Our findings provide new insights into the tumor microenvironment of Hodgkin-like ATLL and implicate a new therapeutic strategy targeting these molecules.
2023-12-06 | GSE213461 | GEO
Project description:The mutational profile of classic Hodgkin lymphoma (cHL) overlaps with that of related B cell lymphomas, including primary mediastinal B cell lymphoma (PMBL), and yet these are different histologically and clinically. To discover the molecular features that distinguish cHL, we deployed flow cytometric cell sorting and low-input RNA sequencing to generate full transcriptome data from viable, isolated Hodgkin and Red-Sternberg (HRS) cells from eighteen primary tumors, alongside matched intra-tumoral non-neoplastic B cells and four cell lines. Comparison of HRS cells to normal cellular subsets revealed evidence of abortive plasma cell differentiation, with an unfolded protein response signature, shared with plasma cell neoplasms, but not other B-cell lymphoma types. Comparison of cHL to PMBL revealed similarities but also key differences in B cell differentiation programs accompanied by upregulation of genes involved in microtubule cytoskeleton organization in cHL, which may be related to the unique multinucleated nature of HRS cells. In HRS cells, we also observed a downregulation of SLAM family receptors, which are crucial for NK cell activation, providing a potential mechanism for immune evasion from NK-mediated killing. New fusion transcripts were seen, including a recurrent transcript predicted to result in an in-frame fusion protein involving TRAF1 and PHF19.
2026-04-13 | GSE301492 | GEO
Project description:Distinct SCLC molecular subtypes have been defined based on expression of lineage-related transcription factors: ASCL1, NEUROD1, POU2F3 or YAP1, but their origins remain unknown. To study transcriptional dynamics of MYC-driven tumor evolution and compare transcriptional states to human SCLC tumors, we performed bulk and single-cell RNA-sequencing on various timepoints of Rb1/Trp53/MycT58A (RPM) tumor cells (from Ad-Cgrp-Cre infected mice) as they progress in culture, and on RPM bulk tumors. Here, to complement these analyses we performed ~30X whole-genome sequencing (WGS) of early (day 4) and late (day 23) time-point RPM tumor cells from culture, along with a matching normal blood control to confirm complete loss of expected regions of Rb1 and Trp53. WGS analyses revealed no detectable copy number variations (CNVs), and SNV analysis suggests that minimal clonal and subclonal evolution occurs in vitro. Together, these data ultimately reveal that MYC drives the dynamic evolution of SCLC subtypes. We find that MYC promotes a temporal shift from an ASCL1-to-NEUROD1-to-YAP1+ state from a neuroendocrine cell of origin. MYC activates Notch signaling to dedifferentiate tumor cells to non-neuroendocrine fates. These findings support our overall conclusions that genetics, cell of origin, and tumor cell plasticity determine SCLC subtype.
2020-05-28 | GSE149444 | GEO
Project description:Classic Hodgkin lymphoma (CHL) harbors a small number of Hodgkin-Reed-Sternberg (HRS) cells scattering among numerous lymphocytes. HRS cells are surrounded by distinct CD4+ T cells in a rosette-like manner. These CD4+ T cell rosettes play an important role in tumor microenvironment (TME) of CHL. To elucidate the interaction between HRS cells and CD4+ T cell rosettes, we performed digital spatial profiling (DSP) and compared gene expression profile between CD4+ T cell rosettes and other CD4+ cells separated from HRS cells. programed cell death-1 (PD-1) and tumor necrosis factor receptor superfamily member (TNFRSF) 4 were significantly highly expressed in CD4+ T cell rosettes than others. Immunohistochemistry confirmed PD-1 and TNFRSF4-expressing CD4+ T cell rosettes. This study introduced the new pathological approach to TME and provided deeper insight to CD4+ T cells in CHL.
2023-07-03 | GSE218703 | GEO
Project description:The pathogenesis of classical Hodgkin lymphoma (cHL), the most common lymphoma in the young, is still enigmatic, largely because its Hodgkin and Reed-Sternberg (HRS) tumor cells are rare in the involved lymph node and therefore difficult to analyze. Here, by overcoming this technical challenge and performing for the first time a genome-wide transcriptional analysis of microdissected HRS cells in comparison to other B-cell lymphomas, cHL lines and normal B-cell subsets, we show that they differ extensively from the usually studied cHL cell lines, that the lost B-cell identity of cHLs is not linked to the acquisition of a plasma cell-like gene expression program, and that Epstein-Barr virus infection of HRS cells has a minor transcriptional influence on the established cHL clone. Moreover, although cHL appears a distinct lymphoma entity overall, HRS cells of its histological subtypes diverged in their similarity to other related lymphomas. Unexpectedly, we identified two molecular subgroups of cHL associated to differential strengths of the transcription factor activity of the NOTCH1, MYC and IRF4 proto-oncogenes. Finally, HRS cells display deregulated expression of several genes potentially highly relevant to lymphoma pathogenesis, including silencing of the apoptosis-inducer BIK and of INPP5D, an inhibitor of the PI3K-driven oncogenic pathway. The present study complements the GSE12453 and GSE14879 records by adding the following 10 samples: 5 primary tumor samples and 5 cell line samples. The 5 primary tumor samples represent 1000-2000 neoplastic cells microdissected from frozen biopsies of 5 cases of primary mediastinal B-cell lymphoma (PMBL). The 5 cell line samples represent 500-1000 living neoplastic cells isolated by fluorescence-activated cell sorting from growing cultures of the classical Hodgkin lymphoma (cHL) cell lines L1236, L428, KMH2 and HDLM2 and the lymphocyte-predominant Hodgkin lymphoma (lpHL) cell line DEV.
2012-09-17 | E-GEOD-40160 | biostudies-arrayexpress
Project description:The pathogenesis of classical Hodgkin lymphoma (cHL), the most common lymphoma in the young, is still enigmatic, largely because its Hodgkin and Reed-Sternberg (HRS) tumor cells are rare in the involved lymph node and therefore difficult to analyze. Here, by overcoming this technical challenge and performing for the first time a genome-wide transcriptional analysis of microdissected HRS cells in comparison to other B-cell lymphomas, cHL lines and normal B-cell subsets, we show that they differ extensively from the usually studied cHL cell lines, that the lost B-cell identity of cHLs is not linked to the acquisition of a plasma cell-like gene expression program, and that Epstein-Barr virus infection of HRS cells has a minor transcriptional influence on the established cHL clone. Moreover, although cHL appears a distinct lymphoma entity overall, HRS cells of its histological subtypes diverged in their similarity to other related lymphomas. Unexpectedly, we identified two molecular subgroups of cHL associated to differential strengths of the transcription factor activity of the NOTCH1, MYC and IRF4 proto-oncogenes. Finally, HRS cells display deregulated expression of several genes potentially highly relevant to lymphoma pathogenesis, including silencing of the apoptosis-inducer BIK and of INPP5D, an inhibitor of the PI3K-driven oncogenic pathway.
2012-09-17 | GSE40160 | GEO
Project description:Hodgkin's lymphoma (HL) is one of the most frequent hematological malignancies. Due to its extraordinary composition, few tumor cells surrounded by a reactive infiltrate, HL can be seen as an ideal model system for research focusing on tumor immunology. In fact, the tumor cells of HL, so called Hodgkin/Reed-Sternberg (HRS) cells attract CD4+ T cells, which then build rosettes with the HRS cells. HRS cells further modulate the tumor microenvironment with the help of CD4+ T cells to avoid tumor rejection. Here, we mimicked this scenario using compatible CD4+ T cells receiveing data of profound interactions for the first time, as former studies were performed with allogeneic donors. Finally, we genetically retargeted compatible CD4+ T cells to kill HRS cells.
2016-11-29 | GSE75267 | GEO
Project description:Classic Hodgkin lymphoma (CHL) harbors a small number of Hodgkin-Reed-Sternberg (HRS) cells scattered among numerous lymphocytes. HRS cells are surrounded by distinct CD4+ T cells in a rosette-like manner. These CD4+ T cell rosettes play an important role in the tumor microenvironment (TME) of CHL. To elucidate the interaction between HRS cells and CD4+ T cell rosettes, we completed digital spatial profiling to compare the gene expression profiles of CD4+ T cell rosettes and other CD4+ T cells separated from the HRS cells. Tumor necrosis factor receptor superfamily member (TNFRSF) 4 or OX40 showed significantly higher expression in CD4+ T cell rosettes when compared with other CD4+ T cells. Programed cell death-1 (PD-1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4) tended to be highly expressed in CD4+ T cell rosettes compared to other CD4+ T cells. Immunohistochemistry revealed variable expression of these immune checkpoint molecules in the CD4+ T cell rosettes. This study introduced a new pathological approach to the TME and provided deeper insight into CD4+ T cells in CHL.
2023-07-03 | GSE227013 | GEO
Project description:CD4 T cells were activated using CD3/CD28 antibodies in the presence of IL2 and IL12, to generate Th1 cells. Th1 cells were maintained and expanded in IL2 and IL12, on D5 Th1 cells were sorted for CD4+ expression and DAP1 exclusion. After flow sorting, live TH1 cells were resuspended (1e6 per ml) in methionine free RPMI, supplemented with 10% dialysed FBS, IL2 and IL12, and with L-methionine (100μM, or 1μM). Cells were cultured for 5 hrs before collection for proteomics processing.
2019-03-29 | PXD012053 | Pride
Project description:The cellular microenvironment in classical Hodgkin lymphoma (cHL) is dominated by a mixed infiltrate of inflammatory cells with typically only about 1% Hodgkin and Reed/Sternberg (HRS) tumor cells. T cells are usually the largest population of cells in the cHL microenvironment, encompassing T helper (Th) cells, regulatory T (Treg) cells and cytotoxic T cells. Th and Treg cells presumably provide essential survival signals for HRS cells. Treg cells are also involved in rescuing HRS cells from anti-tumor immune responses. An understanding of the immune evasion strategies of HRS cells is not only highly relevant for a characterization of the pathophysiology of cHL, but also clinically, given the current treatment approaches targeting checkpoint inhibitors. Here, we characterized the cHL-specific CD4+ T cell infiltrate regarding its role in immune evasion. Global gene expression analysis of CD4+ Th and Treg cells isolated from cHL lymph nodes and reactive tonsils revealed that Treg cell signatures were enriched in CD4+ Th cells of cHL. Hence, HRS cells may induce a Treg differentiation in Th cells, which was supported by in vitro studies with Th cells and cHL cell lines. Furthermore, we found indication for immune-suppressive purinergic signaling and a role of the inhibitory receptor-ligand pairs BTLA-HVEM and CD200R-CD200 in promoting immune evasion. Taken together, this study reveals that the immune evasion strategies in cHL are even more complex and multifaceted than previously recognized.
2017-10-09 | GSE102693 | GEO