Gene expression signature of ex vivo expanded NK cells for 14 days
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE166933 | GEO | 2021/10/27
REPOSITORIES: GEO
Similar Datasets
Project description:We performed RNA sequencing to employ an unbiased approach to identify the altered gene expression enhancing the function of ex vivo expanded pNK cells for 14 days, and transcriptionally compared day 0 and day 14 pNK cells.
2021-10-27 | GSE163538 | GEO
Project description:Gene expression signature of ex vivo expanded NK cells for 14 days
| PRJNA702438 | ENA
Project description:Gene expression signature of ex vivo expanded NK(CD3-CD56+) cells for 14 days
| PRJNA686645 | ENA
Project description:The final goal of this study is to develop a short term and highly accurate prediction method of carcinogenicity based on gene expression profiles of rats subjected to carcinogen exposure. We conducted 3 day-, 14 day- and 28 day-repeated dose experiments in male F344 rats with 47 carcinogens and 26 non-carcinogens, and the gene expression profiles in liver were investigated by custom glass microarrays. Supplementary file "73 Compounds for training" indicates 47 carcinogens and 26 non-carcinogens. Supplementary file "15 Compounds for test" lists the other compounds which are for test.
2009-06-23 | GSE16743 | GEO
Project description:Purpose: Daratumumab and its use in combination with other agents is becoming a new standard of care for the treatment of multiple myeloma. We mechanistically studied how daratumumab acts on natural killer (NK) cells.Experimental Design: Quantities of NK cells in peripheral blood and/or bone marrow of patients with multiple myeloma or healthy donors were examined by flow cytometry. NK-cell apoptosis and the associated mechanism were assessed by flow cytometry and immunoblotting. Patients' NK cells were expanded in vitro using feeder cells. Combination treatment of daratumumab and expanded NK cells was performed using an MM.1S xenograft animal model.Results: CD38-/low NK cells survived, whereas CD38+ NK cells were almost completely eliminated, in peripheral blood and bone marrow of daratumumab-treated multiple myeloma patients. NK-cell depletion occurred due to daratumumab-induced NK-cell fratricide via antibody-dependent cellular cytotoxicity. Consequently, CD38-/low NK cells were more effective for eradicating multiple myeloma cells than were CD38+ NK cells in the presence of daratumumab. Blockade of CD38 with the F(ab)2 fragments of daratumumab inhibited the antibody-mediated NK-cell fratricide. CD38-/low NK cells displayed a significantly better potential for expansion than CD38+ NK cells, and the expanded NK cells derived from the former population were more cytotoxic than those derived from the latter against multiple myeloma cells. Therefore, infusion of ex vivo-expanded autologous NK cells from daratumumab-treated patients may improve the antibody therapy.Conclusions: We unravel a fratricide mechanism for daratumumab-mediated NK-cell depletion and provide a potential therapeutic strategy to overcome this side effect in daratumumab-treated patients with multiple myeloma. Clin Cancer Res; 24(16); 4006-17. ©2018 AACR.
| S-EPMC6095810 | biostudies-literature
Project description:Background aimsSeveral methods to expand and activate (EA) NK cells ex vivo have been developed for the treatment of relapsed or refractory cancers. Infusion of fresh NK cells is generally preferred to the infusion of cryopreserved/thawed (C/T) NK cells because of concern that cryopreservation diminishes NK cell activity. However, there has been little head-to-head comparison of the functionality of fresh versus C/T NK cell products.MethodsWe evaluated activity of fresh and C/T EA NK cells generated by interleukin (IL)-15, IL-2 and CD137L expansion.ResultsAnalysis of C/T NK cell products demonstrated decreased recovery of viable CD56+ cells, but the proportion of NK cells in the C/T EA NK cell product did not decrease compared with the fresh EA NK cell product. Fresh and C/T EA NK cells demonstrated increased granzyme B compared with NK cells pre-expansion, but only fresh EA NK cells showed increased NKG2D. Compared with fresh EA NK cells, cytotoxic ability of C/T EA NK cells was reduced, but C/T EA NK cells remained potently cytotoxic against tumor cells via both antibody-independent and antibody-dependent mechanisms within 4 h post-thaw. Fresh EA NK cells generated high levels of gamma interferon (IFN-γ), which was abrogated by JAK1/JAK2 inhibition with ruxolitinib, but C/T EA NK cells showed lower IFN-γ unaffected by JAK1/JAK2 inhibition.DiscussionUsage of C/T EA NK cells may be an option to provide serial "boost" NK cell infusions from a single apheresis to maximize NK cell persistence and potentially improve NK-induced responses to refractory cancer.
| S-EPMC7387178 | biostudies-literature
Project description:pNK treatment with a combination of TGFb, 5-aza-2’-deoxycytidine and hypoxia yields cells with functional and phenotypic similarities to human dNK cells, called induced dNK-like cells (idNK)
2016-10-14 | GSE85592 | GEO
Project description:The infusion of natural killer (NK) cells is a promising therapy for patients with advanced malignancies. Clinical expanded NK-cell products were compared with freshly isolated NK cells. Autologous peripheral blood mononuclear cells were collected by apheresis from 8 patients. NK cells were isolated by anti-CD3-negative selection followed by anti-CD56-positive selection. They were then expanded by co-culture with interleukin-2 and an irradiated Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line (EBV-TM-LCL) to produce 14 NK-cell products. Molecular changes in the 14 NK-cell products were characterized using gene and microRNA expression microarrays. EBV-TM-LCL feeder cells from 3 lots were also analyzed as they were expanded for over 90 days and each lot was used for multiple NK-cell expansions. The gene expression profiles among the 3 EBV-TM-LCL lots used showed no differences and were not affected by their time in culture. Freshly isolated and expanded NK cells had distinct gene and microRNA expression profiles. Compared with fresh NK cells, expanded NK cells overexpressed 1098 genes and 28 human microRNAs. Genes in the crosstalk between dendritic and NK cells and metabolic pathways were up-regulated in expanded NK cells, whereas genes in a number of immune function pathways were down-regulated. Among all the most up-regulated genes were the NK cell-activating receptor natural cytotoxicity triggering receptor 3, myxovirus restistance 1, lymphotoxin ?, and BCL2-associated X protein. Although some expanded NK-cell product variability was observed, perhaps related to patient factors, further studies on larger numbers of products will be needed to determine the impact of these differences on clinical outcomes.
| S-EPMC3096009 | biostudies-other
Project description:The final goal of this study is to develop a short term and highly accurate prediction method of carcinogenicity based on gene expression profiles of rats subjected to carcinogen exposure. We conducted 3 day-, 14 day- and 28 day-repeated dose experiments in male F344 rats with 47 carcinogens and 26 non-carcinogens, and the gene expression profiles in liver were investigated by custom glass microarrays. Supplementary file "73 Compounds for training" indicates 47 carcinogens and 26 non-carcinogens. Supplementary file "15 Compounds for test" lists the other compounds which are for test. Two-condition experiment, control vs. chemical treated rat liver. Biological replicates: 4 control, 4 treated, control samples were pooled. One replicate per array.
2009-06-23 | E-GEOD-16743 | biostudies-arrayexpress
Project description:To investigate novel molecular signatures and transcriptional regulators of immature and mature human NK cells, we performed whole-genome microarray analysis on dNK cells (CD3−CD56+), cNK cells (CD3−CD56+), pNK cells (CD3−CD56+), CD56+ T cells (CD3+CD56+) and T cells (CD3+CD56−). dNK cells were purified from first-trimester deciduas. cNK cells were purified from cord-blood mononuclear cells. pNK, CD56+ T and T cells were purified from adult peripheral blood mononuclear cells. Samples were collected from healthy adult donors after obtaining informed consent according to the Ethics Committee of the University of Science & Technology of China.
2013-02-10 | GSE24268 | GEO