Transcriptome Analysis of Basal NK Cells and Different NKAE Cell Products
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE165849 | GEO | 2021/02/16
REPOSITORIES: GEO
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Project description:Natural Killer cells (NK), a major constituent of innate immune system, have the ability to kill the transformed and infected cells without prior sensitization; can be put to immunotherapeutic use against various malignancies. NK cells discriminate between normal cells and transformed cells via a balance of inhibitory and activating signals induced by interactions between NK cell receptors and target cell ligands. Present study investigates whether expansion of NK cells could augment their anti-myeloma (MM) activity. For NK cell expansion, peripheral blood mononuclear cells from healthy donors and myeloma patients were co-cultured with irradiated K562 cells transfected with 4-1BBL and membrane-bound IL15 (K562-mb15-41BBL). A genome-wide profiling approach was performed to identify gene expression signature in expanded NK (ENK) cells and non-expanded NK cells isolated from healthy donors and myeloma patients. A specific set of genes involved in proliferation, migration, adhesion, cytotoxicity, and activation were up regulated post expansion, also confirmed by flow cytometry. Exp-NK cells killed both allogeneic and autologous primary MM cells more avidly than non-exp-NK cells in vitro. Multiple receptors, particularly NKG2D, natural cytotoxicity receptors, and DNAM-1 contributed to target lysis, via a perforin mediated mechanism. In summary, vigorous expansion and high anti-MM activity both in vitro and in vivo provide the rationale for testing exp-NK cells in a clinical trial for high risk MM. Differential gene expression profile in expanded natural killer (ENK) cells and non-expanded natural killer (NK) cells from healthy donors and myeloma patients Eight healthy donor and eight myeloma patients were used in the study. Non-expanded natural killer (NK) cells were isolated from PBMCs of healthy donors and myeloma patients. Expanded natural killer (ENK) cells were generated from same set of samples as mentioned in expansion protocol. All ENK and NK cells were used for gene expression profiling.
2011-03-08 | E-GEOD-27838 | biostudies-arrayexpress
Project description:Transcriptome Analysis of Basal NK Cells and Different NKAE Cell Products
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Project description:NK cells are cytotoxic lymphocytes that play an important role in the innate immune response. The immune response of NK cells was shown under activated conditions. In order to identify such patterns, we performed RNA sequencing to confirm the gene expression profiles in NK cells expanded ex vivo compared to that of resting NK cells.
2023-05-17 | GSE222740 | GEO
Project description:Genome editing human NK cells expanded from human peripheral blood.
2023-05-02 | GSE229085 | GEO
Project description:Natural Killer cells (NK), a major constituent of innate immune system, have the ability to kill the transformed and infected cells without prior sensitization; can be put to immunotherapeutic use against various malignancies. NK cells discriminate between normal cells and transformed cells via a balance of inhibitory and activating signals induced by interactions between NK cell receptors and target cell ligands. Present study investigates whether expansion of NK cells could augment their anti-myeloma (MM) activity. For NK cell expansion, peripheral blood mononuclear cells from healthy donors and myeloma patients were co-cultured with irradiated K562 cells transfected with 4-1BBL and membrane-bound IL15 (K562-mb15-41BBL). A genome-wide profiling approach was performed to identify gene expression signature in expanded NK (ENK) cells and non-expanded NK cells isolated from healthy donors and myeloma patients. A specific set of genes involved in proliferation, migration, adhesion, cytotoxicity, and activation were up regulated post expansion, also confirmed by flow cytometry. Exp-NK cells killed both allogeneic and autologous primary MM cells more avidly than non-exp-NK cells in vitro. Multiple receptors, particularly NKG2D, natural cytotoxicity receptors, and DNAM-1 contributed to target lysis, via a perforin mediated mechanism. In summary, vigorous expansion and high anti-MM activity both in vitro and in vivo provide the rationale for testing exp-NK cells in a clinical trial for high risk MM. Differential gene expression profile in expanded natural killer (ENK) cells and non-expanded natural killer (NK) cells from healthy donors and myeloma patients
2011-03-08 | GSE27838 | GEO
Project description:Natural Killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in the research and clinical trials. Clinical observations witnessed the improvement of patients’ NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug against CML and Ph+ ALL. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well-defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)-NK cells. By coculturing NK cells with dasatinib to test the cell counts and target cell killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB-NK killing tumor cells. RNA-seq analysis further supported this finding, uncovering several proliferating and cytotoxic pathways were responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB-NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.
2023-10-17 | GSE245219 | GEO
Project description:NK cells are lymphocytes that provide a first defense against viral infections and cancer. They act (i) cytotoxic by killing virus-infected and tumorigenic cells and (ii) immune regulatory by releasing cytokines and chemokines. These innate immune cells are commonly further classified as CD56bright and CD56dim NK cells. Former studies confirmed immune regulatory CD56bright NK cells as progenitors of cytotoxic CD56dim NK cells. CD57 was previously described as T cell marker for senescence and terminal differentiation. Recent studies detected CD57+ and CD57- NK cells among the CD56dim NK cell population and suggested a fully mature developmental status for CD57+ NK cells. The recent NK cell maturation model includes CD34+ hematopoietic stem cells (HSC), which develop into CD56bright NK cells, later into CD56dimCD57- and finally into terminally maturated CD56dimCD57+ (1) (2) (3). The molecular mechanisms of human NK cell differentiation and maturation remain unknown to this date. We performed for the first time a proteomic analysis of these distinct developmental stages of human primary NK cells, isolated from overall 10 healthy human blood donors. CD56bright NK cells versusCD56dim and CD56dimCD57- versus CD56dimCD57+ NK cells were analyzed by using quantitative peptide sequencing, which revealed individual protein signatures (3400 proteins) of these different NK cell developmental stages. Notably, our data support the current NK cell differentiation model by highlighting both strong distinctions between CD56dim/bright NK cells and close relationships between CD57+/- NK cells on the proteomic level. Among the most prominent and conserved regulated proteins, we detected myosin IIa, Calvasculin and Calcyclin with very similar expression patterns. We investigated their sub-cellular localization and observed specific recruitment- and accumulation-events at the NK cell immunological synapse (NKIS) after NK activation.
2013-01-23 | PRD000666 | Pride
Project description:With mass spectrometry， we aim to find the differentially expressed proteins in Mettl3-deficient NK cells
2021-07-20 | PXD025823 | iProX
Project description:A study of immunotherapy with expanded CB-NK cells in combination with cetuximab, to evaluate activity against minimal residual disease in patients with colon cancer that have completed adjuvant treatment but are positive for ctDNA
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Project description:Ex vivo activation and expansion of natural killer (NK) cells is a strategy to produce sufficient numbers of these effector cells for adoptive immunotherapy. Therefore we aimed at the development of an automated, clinical scale NK cell expansion process and compared NK cells after manual and automated expansion.We found only a small subset of 124 genes that significantly varied between both sample groups. These genes were associated with movement of leukocytes were identified including a group of genes for NK cell movement (CMKLR1, CX3CR1, S1PR5, GNLY and CXCR1) which were slightly higher expressed after automated compared to manual expansion. Nevertheless, the expansion profiles of NK cells after automated or manual expansion were rather similar in comparison to the remarkable difference between primary and expanded NK cells in general represented by the vast majority of regulated genes between the analyzed sample groups. Pathway analysis revealed that most of regulated genes upon expansion were associated with cell cycle regulation, DNA replication, DNA recombination and DNA repair, regulation of apoptosis and cell survival as well as cytokine signaling. Furthermore, the expression of many NK cell relevant markers was changed upon expansion with the strongest effects on up regulation of TRAIL and FASL, inhibitory TIGIT and chemokine receptors CCR2, CCR5 and CXCR6. In addition, granzyme M was down regulated but other important effector molecules like TNFa, perforin and granzymes A, B and K were up regulated. In summary we could show that manual and automatically expanded NK cells show a similar expansion profile while the differ significantly from primary NK cells. Up regulation of many NK cell relevant markers indicate for an enhanced NK cell functionaility after ex vivo activation and expansion. 24 samples were analyzed in total. 6 biological replicates represented by cells from different donors. 4 different samples per donor: freshly isolated NK cells (d0) and NK cells expanded for 14 days under 3 different conditions: in co-culture with EBV-LCL feeder cells and 500 U/mL IL2 either cultivated manually in T75 flasks (T) or automatically using the CliniMACS Prodigy system (P); NK cells cultured with 500 U/ml IL2 without feeder cells (I)
2015-04-23 | E-GEOD-62654 | biostudies-arrayexpress