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Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells.

ABSTRACT: To examine the impact of tumors on the immune system, we compared global gene expression profiles of peripheral blood T cells from previously untreated patients with B cell chronic lymphocytic leukemia (CLL) with those from age-matched healthy donors. Although the cells analyzed were not part of the malignant clone, analysis revealed differentially expressed genes, mainly involved in cell differentiation in CD4 cells and defects in cytoskeleton formation, vesicle trafficking, and cytotoxicity in CD8 cells of the CLL patients. In coculture experiments using CLL cells and T cells from healthy allogeneic donors, similar defects developed in both CD4 and CD8 cells. These changes were induced only with direct contact and were not cytokine mediated. Identification of the specific pathways perturbed in the T cells of cancer-bearing patients will allow us to assess steps to repair these defects, which will likely be required to enhance antitumor immunity. Gene expression profiling was performed to determine whether CLL cells induce changes in T cells in patients with CLL. Keywords: comparative gene expression profiling analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE8835 | GEO | 2007/08/22

SECONDARY ACCESSION(S): PRJNA102171

REPOSITORIES: GEO

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Transcription profiling of human CD4 T cells and CD8 T cells were obtained from peripheral blood mononuclear cells of previously untreated patients with CLL and healthy individuals reveals chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells.

Project description:To examine the impact of tumors on the immune system, we compared global gene expression profiles of peripheral blood T cells from previously untreated patients with B cell chronic lymphocytic leukemia (CLL) with those from age-matched healthy donors. Although the cells analyzed were not part of the malignant clone, analysis revealed differentially expressed genes, mainly involved in cell differentiation in CD4 cells and defects in cytoskeleton formation, vesicle trafficking, and cytotoxicity in CD8 cells of the CLL patients. In coculture experiments using CLL cells and T cells from healthy allogeneic donors, similar defects developed in both CD4 and CD8 cells. These changes were induced only with direct contact and were not cytokine mediated. Identification of the specific pathways perturbed in the T cells of cancer-bearing patients will allow us to assess steps to repair these defects, which will likely be required to enhance antitumor immunity. Gene expression profiling was performed to determine whether CLL cells induce changes in T cells in patients with CLL. Experiment Overall Design: CD4 T cells and CD8 T cells were obtained from peripheral blood mononuclear cells of previously untreated patients with CLL and healthy individuals. Gene expression profiling was performed using total RNA and the data were analysed to compare gene expression profile of T cells from patients with CLL to healthy individuals .

2008-06-16 | E-GEOD-8835 | biostudies-arrayexpress

Transcription profiling of mouse model of CLL in Em-TCL1 mice provides a biologically relevant model to unravel and reverse immune deficiency in human cancer.

Project description:Immune deficiency is common in cancer, but the biological basis for this and ways to reverse it remains elusive. Here we present a mouse model of B cell chronic lymphocytic leukemia (CLL) that recapitulates changes in the non-malignant circulating T cells seen in patients with this illness.1 To validate this model, we examined changes in T cell gene expression, protein expression and function in Em-TCL1 transgenic mice as they developed CLL 2,3 and demonstrate that development of CLL in these transgenic mice is associated with changes in impaired T cell function and in gene expression in CD4 and CD8 T cells similar to those observed in patients with this disease. Infusion of CLL cells into non-leukemia bearing Em-TCL1 mice rapidly induces these changes, demonstrating a causal relationship between leukemia and the induction of T cell changes. This model allows dissection of the molecular changes induced in CD4 and CD8 T cells by interaction with leukemia cells and further supports the concept that cancer results in complex abnormalities in the immune microenvironment. Gene expression profiling was performed to determine whether Em-TCL1 murine model of chronic lymphocytic leukemia (CLL) mimics T cell defects induced by CLL cells in patients with CLL. Experiment Overall Design: CD4 T cells and CD8 T cells were obtained from spleens of B6C3 and Em-TCL1 transgenic murine model of CLL or from peripheral blood mononuclear cells of previously untreated patients with CLL and healthy individuals (Pubmed ID: 15965501). Gene expression profiling was performed using total RNA and the data were analysed to compare gene expression profile of CLL to healthy within or between the species.

2008-06-17 | E-GEOD-8836 | biostudies-arrayexpress

Dysregulation of different classes of tRNA fragments in chronic lymphocytic leukemia

Project description:We analyzed small RNA sequencing data from CD5+/CD19+ B cells of a cohort of indolent and aggressive CLL patients compared with CD19+ B-cells of healthy donors. We identified tsRNA signatures in indolent and aggressive CLL vs. normal B-cells; we also found a drastic dysregulation of the expression of mature tRFs in CLL.

2019-11-11 | GSE138889 | GEO

Transcription profiling of human T cells from patients presenting with AML compared with healthy T cells

Project description:Work previously published by our group has demonstrated that T cells from patients with chronic lymphocytic leukaemia (CLL) show differentially regulated genes compared with healthy T cells. This study was initiated to examine if these gene expression changes were unique to CLL T cells or common to an alternative leukaemia, acute myeloid leukaemia (AML). Experiment Overall Design: The study was composed of four groups of samples: AML CD4 (n=10), AML CD8 (n=10), Healthy CD4 (n=10), Healthy CD8 (n=11). AML samples were chosen to represent the range of FAB types, prognostic groups and patient outcomes. Healthy T cells were obtained from volunteers. The purity of isolated T cell fractions was greater than 70% in all cases.

2009-06-01 | E-GEOD-14924 | biostudies-arrayexpress

Genome-wide analysis of impact of B cells from the peripheral blood of chronic lymphocytic leukemia (CLL) patients versus B cells from healthy donors on CD14+ PBMCs from healthy donors

Project description:CD14+ cells in the PBMCs of CLL patients are converted into NLCs. CD14+ PBMCs from healthy donors when cultured with CLL cells give rise to differentiated cells called CD14CLL-cells, which are immunophenotypically similar to NLCs. CD14+ PBMCs from healthy donors when cultured with non-malignant B cells give rise to differentiated cells called CD14B-cells. Transcriptome wide analysis reveals genes involved in immune response to be significantly deregulated between CD14B-cells and CD14CLL-cells/NLCs.

2013-01-01 | GSE21838 | GEO

T-Cells from CLL patients

Project description:T cells may have a role in sustaining the leukemic clone in chronic lymphocytic leukemia (CLL). In this study, we have examined the ability of T cells from CLL patients to support the survival of the leukemic B cells in vitro. Additionally, we compared global gene expression of T cells from indolent CLL patients with healthy individuals and multiple myeloma (MM) patients. Apoptosis of purified CLL cells was inhibited in vitro when cocultured with increasing numbers of autologous T cells (p<0.01) but not with normal donors. The anti-apoptotic effect exceeded that of the antiapoptotic cytokine IL-4 (p=0.02) and was greater with CD8+ T cells than with CD4+ cells (p<0.05). The effect depended mainly on cell-cell contact although a significant effect was observed in transwell experiments (p<0.05). Additionally, about 356 genes involved in different cellular pathways were deregulated in T cells of CLL patients compared to healthy individuals and MM patients. The results of gene expression profiling was verified for 7 genes (KLF6, TRAF1, CCL4, CCL5, RANTES, XCL1 and XCL2) using qRT-PCR and immunoblotting. Our results demonstrate that CLL-derived T cells can prevent apoptosis of leukemic cells and have altered expression of genes that may facilitate survival of the leukemic clone. Peripheral blood was collected by venipuncture from CLL patients, multiple myeloma (MM) patients and age-matched healthy individuals with informed consent and approval of the local Ethics Committee in keeping with the Helsinki declaration on the use of human subjects for research.

2011-03-23 | E-GEOD-28107 | biostudies-arrayexpress

Effects of lenalidomide treatment on CAR-redirected T cells derived from CLL patients

Project description:Significant response rates have been reported in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphomas (DLBCL), mantle cell lymphomas and follicular lymphomas. In contrast, in CTL019 trials, only 26% of CLL patients had durable antitumor responses with dramatic mechanisms of resistance to anti-CD19.CAR T-cell therapy. Low expression of programmed cell death protein 1 (PD1) has been identified as pre-treatment predictor of response in these trials, though the mechanisms responsible for a limited efficacy in CLL remain poorly understood. Additional studies have demonstrated that CD8+ anti-CAR T cells from patients with CLL exhibit impaired metabolic function compared to CD8+ T cells from healthy donors and that these features are associated with T-cell exhaustion and a reduction in T-cell activation and degranulation. Several T-cell defects have been observed in patients with CLL and are mainly related to impaired immune synapse (IS) formation, and these defects could ultimately impact on the CAR T-cell activation and expansion upon antigen encounter. Thus, the purpose of this study was to explore the possibility of using lenalidomide, an immunomodulatory agent that has induced significant, long-lasting responses in CLL patients, to enhance the therapeutic efficacy of CD23.CAR-redirected T cells.

2022-02-28 | GSE178893 | GEO

Gene expression profiles of monocytes derived from chronic lymphocytic leukemia patients and normal controls

Project description:We collected monocytes from peripheral blood of 5 chronic lymphocytic leukemia (CLL) patients and 5 healthy donors and we performed gene expression analysis by microarray. Comparison of gene expression profiles (GEPs) between CLL-derived and normal monocytes was used to discover molecular abnormalities in this nonmalignant immune cellular population in leukemia-bearing patients. Although analysed cells were not part of the malignant clone, in unsupervised hierarchical clustering analysis, GEPs of normal monocytes were clearly distinguishable from those of monocytes obtained from CLL patients. Supervised analysis identified 65 genes significantly up-regulated and 48 genes down-regulated in CLL monocytes compared with monocytes from normal controls (FC=2, p<0.05). Modification of gene expression profile would imply impairment of phagocytosis and production of immunosuppressive mediators in CLL-derived monocytes. The alterations described in our study further contribute to characterize the complexity of factors potentially involved in acquired immune deficiency of CLL patients.

2013-01-10 | GSE35179 | GEO

T lymphocytes from Chronic HCV-infected patients express unique pro-apoptotic gene signature.

Project description:Although extensive studies have demonstrated the gene expression patterns of antigen-specific CD4+ and CD8+ T-cells during chronic hepatitis C virus (HCV) infection, the transcriptional profiles of global CD4+ and CD8+ T-cells remains unclear. In this report, we recruited 10 long-term (~20 years) treatment-naM-CM-/ve chronic HCV (CHC) patients and 5 healthy donors (HDs) to investigate differences in global CD4+ and CD8+ T-cells gene expression profile. Global CD4+ and CD8+ T-cells showed unique transcriptional profiles in the expression of apoptosis-related genes. We identified BCL2, PMAIP1, and CASP1 in CD4+ T-cells and IER3 and BCL2A1 in CD8+ T-cells from CHC patients as HCV-specific gene signatures. The unique apoptosis-related gene expression profilesin global CD4+ and CD8+ T-cells programmed by chronic HCV infection seemed to enhance activation-induced apoptosis, which was suffered by global CD4+ and CD8+ T-cells. We obtained 15 blood samples to identify the gene expression signatures of global CD4+ and CD8+ T-cells due to chronic HCV infection. The samples included: 5 samples from high HCV viral load patients (HCV-h), 5 samples from low HCV viral load (HCV-l) and 5 samples from healthy donors (HD). HCV patients were all Ab+ and treatment-naive prior to the study. Samples were taken once from each individual. Global CD4+ and CD8+ T-cells were enriched by microbeads, and total RNA were used in gene chip analysis.

2013-08-19 | E-GEOD-49954 | biostudies-arrayexpress

T-Cells from CLL patients

2011-03-24 | GSE28107 | GEO

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