Effects of lenalidomide treatment on CAR-redirected T cells derived from CLL patients
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ABSTRACT:
PROVIDER: PRJNA741468 | ENA |
REPOSITORIES: ENA
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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
Project description:Transcriptom-wide RNA expression profilng in human CAR-T cells treated with lenalidomide in the presense or absense of Ag-specific restimulation
2019-07-16 | GSE113281 | GEO
Project description:Genome-wide DNA accessibility maps of chromatin state in human CAR-T cells treated with lenalidomide in the presense or absense of Ag-specific restimulation
2019-07-16 | GSE113853 | GEO
Project description:The aim of the study is to identify differentially expressed genes between chronic lymphocytic leukemia (CLL) patients who will respond to lenalidomide treatment and non responsive patients. We performed a whole genome gene-expression analysis of pre-treatment samples collected from 16 CLL patients included in a phase II clinical trial. The pre-treatment sample comprises purified CD19 cells from peripheral blood. Ten (37%) patients achieved partial responses (PR) and were classified as responders (R), 2 (7%) stable diseases (SD) and 4 (15%) progressive diseases (PD) and were classified as non responders (NR). Supervised analysis identified 78 genes up-regulated and 119 genes down-regulated in R compared with NR (Fold change [FC]≥2, p<0.01, Figure 4). Different expression levels of genes involved in interferon (INF) and Wnt signaling pathways characterized patients who will respond to lenalidomide. In particular, R showed a 23-fold increase in Wnt inhibitor Shisa homolog 3 (SHISA3), whereas a decrease of WISP3, CDH4, HOXB7 and WNT10A. Moreover, leukemic cells collected from R down-regulated interferon-induced proteins (IFI44, -6.6; IFI44L, -9.3; IFIT2, -2) and STAT1 (-2.4 fold change). NR group up-regulated lipoprotein lipase (LPL, +7.5). The baseline expression levels of cereblon (CRBN) were not dissimilar between R and NR subsets
2017-10-12 | GSE87910 | GEO
Project description:ATACSeq - human CAR-T cells treated with lenalidomide
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Project description:RNASeq: lenalidomide-treated anti-BCMA CAR T cells
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Project description:Gene expression profiles of OSU-CLL cells were tested after exposure to CC-122 (0.1 and 1 micromolar), Lenalidomide (1 micromolar), or DMSO, at 5 and 24 hours
2021-06-04 | GSE115328 | GEO
Project description:Immune stimulation contributes to lenalidomide’s anti-tumor activity. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature, autoreactive B cells in secondary lymphoid tissues, blood and bone marrow and progressive immune dysfunction. Previous studies in CLL indicated that lenalidomide can repair defective T-cell function in vitro. Whether T-cell activation is required for clinical response to lenalidomide remains unclear. Here we report changes in the immune microenvironment in patients with CLL treated with single-agent lenalidomide and associate the immunologic effects of lenalidomide with anti-tumor response. Within days of starting lenalidomide, CD3+ cells increased in the tumor microenvironment and showed Th1-type polarization. Gene expression profiling of pre-treatment and on-treatment lymph node biopsies revealed upregulation of IFN and many of its target genes in response to lenalidomide. The IFNγ-mediated Th1 response was limited to patients achieving a clinical response defined by a reduction in lymphadenopathy. Deep sequencing of T-cell receptor genes revealed decreasing diversity of the T-cell repertoire and an expansion of select clonotypes in responders. To validate our observations, we stimulated T cells and CLL cells with lenalidomide in culture and detected lenalidomide-dependent increases in T-cell proliferation. Taken together, our data demonstrate that lenalidomide induced Th1 immunity in the lymph node that is associated with clinical response.
2018-07-25 | GSE112953 | GEO
Project description:NLCs were generated in vitro by culturing PBMCs from CLL patients for 10 days with/without the addition of 0.5 µM lenalidomide. Then, nonadherent cells were removed by vigorous pipetting and the remaining adherent cells were harvested for analyses. We inspected the whole-genome gene expression profiles of NLCs (control sample vs. lenalidomide-treated sample) derived from 4 CLL patients by microarray. Supervised analysis identified 584 genes differentially expressed upon lenalidomide treatment, 352 up-regulated and 232 down-regulated (p<0.05).
2014-11-24 | GSE57861 | GEO
Project description:NLCs were generated in vitro by culturing PBMCs from CLL patients for 10 days with/without the addition of 0.5 µM lenalidomide. Then, nonadherent cells were removed by vigorous pipetting and the remaining adherent cells were harvested for analyses. We inspected the whole-genome gene expression profiles of NLCs (control sample vs. lenalidomide-treated sample) derived from 4 CLL patients by microarray. Supervised analysis identified 584 genes differentially expressed upon lenalidomide treatment, 352 up-regulated and 232 down-regulated (p<0.05). RNA was extracted with the RNeasy Plus Mini kit (Qiagen, Valencia, CA, USA). Large-scale gene expression profiling (GEP) was performed by hybridizing RNA from NLCs treated or not with lenalidomide 0.5 µM for 10 days (n=4) on 4X44K Whole Human Genome Microarray (Agilent Technologies, Palo alto, CA). Genes were defined as differentially expressed between groups (NLCs CTRL vs. NLCs LENALIDOMIDE) at p<0.05 (paired t-test) and fold change ± 1.5 by using Gene Spring GX v12.6 (Agilent) software.
2014-11-24 | E-GEOD-57861 | biostudies-arrayexpress