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IPSC-derived NK cells and anti-PD-1 antibody synergize to enhance T cell cytokine and cytolytic responses against multiple tumors

ABSTRACT: iPSC-derived NK cells and anti-PD-1 antibody synergize to enhance T cell cytokine and cytolytic responses against multiple tumors

PROVIDER: PRJNA660955 | ENA |

REPOSITORIES: ENA

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iPSC-derived NK cells and anti-PD-1 antibody synergize to enhance T cell cytokine and cytolytic responses against multiple tumors

Project description:We have developed a robust and efficient manufacturing system for the differentiation and expansion of high-quality NK cells (iNKs) derived from induced pluripotent stem cells (iPSCs). We used GeneChip microarrays to compare the whole transcriptome of iNK cells to the transcriptomes of primary T cell and NK cell populations, K562 feeder cell-expanded primary NK cells, fibroblasts, iPSCs and iCD34+ cells.

2020-11-11 | GSE157327 | GEO

Cytokine-enhanced cytolytic activity of Exosomes from NK Cells [small RNA seq]

Project description:Cytokine-enhanced cytolytic activity of Exosomes from NK Cells [small RNA seq]

| PRJNA631792 | ENA

Cytokine-enhanced cytolytic activity of Exosomes from NK Cells

Project description:Natural killer (NK) cells are a type of innate lymphocytes that play key roles in immune surveillance against tumors and viral infection. NK cells distinguish abnormal cells from healthy cells by cell-cell interaction with cell surface proteins and then attack target cells via multiple mechanisms involving TRAIL, Fas Ligand, cytokine secretion, perforin, and granzymes. In addition, extracellular vesicles (EVs), including exosomes derived from NK cells (NK-EVs), possess cytotoxic capacity against tumor cells, but their characteristics and regulation by cytokines remain unknown. Here, we report that EVs derived from human NK-92 cells stimulated with IL-15 + IL-21 show enhanced cytotoxic capacity against tumor cells in a granzyme B independent manner. In addition, small RNA-seq and mass spectrometry analyses indicate that miRNA and protein profiles in EVs are altered by cytokine stimulation. We also show NK-EVs are taken up by target cells via macropinocytosis. Collectively, our findings reveal novel characteristics of NK-EVs and the mechanism of their incorporation into target cells.

2021-09-09 | PXD018982 | Pride

Cytokine-enhanced cytolytic activity of Exosomes from NK Cells [small RNA seq]

2021-05-01 | GSE150342 | GEO

Cytokine-enhanced cytolytic activity of exosomes from NK Cells.

Project description:Natural killer (NK) cells play key roles in immune surveillance against tumors and viral infection. NK cells distinguish abnormal cells from healthy cells by cell-cell interaction with cell surface proteins and then attack target cells via multiple mechanisms. In addition, extracellular vesicles (EVs) derived from NK cells (NK-EVs), including exosomes, possess cytotoxic capacity against tumor cells, but their characteristics and regulation by cytokines remain unknown. Here, we report that EVs derived from human NK-92 cells stimulated with IL-15 + IL-21 show enhanced cytotoxic capacity against tumor cells. Major cytolytic granules, granzyme B and granzyme H, are enriched by IL-15 + IL-21 stimulation in NK-EVs; however, knockout experiments reveal those cytolytic granules are independent of enhanced cytotoxic capacity. To find out the key molecules, mass spectrometry analyses were performed with different cytokine conditions, no cytokine, IL-15, IL-21, or IL-15 + IL-21. We then found that CD226 (DNAM-1) on NK-EVs is enriched by IL-15 + IL-21 stimulation and that blocking antibodies against CD226 reduced the cytolytic activity of NK-EVs. We also show NK-EVs are taken up by target cells via macropinocytosis. Collectively, our findings elucidate the novel properties of NK-EVs and the mechanism of their incorporation into target cells.

| S-EPMC9209332 | biostudies-literature

Mouse cytokine antibody array

Project description:Tumors of hematopoietic stem cell transplantation (HSCT) or control mice were collected at day 14 post transplantation. Comprehensive analysis of cytokine levels were performed by using commercially available RayBio Mouse Cytokine Array G series III and IV (RayBiotech, Inc.) according to manufacturerM-^As protocol. There are two samples: non-HSCT control group and HSCT group. Each group consists of 2 replications.

2013-08-28 | E-MTAB-1761 | biostudies-arrayexpress

Lupus IgA1 autoantibodies synergize with IgG to enhance pDC responses to RNA-containing immune complexes

Project description:Lupus IgA1 autoantibodies synergize with IgG to enhance pDC responses to RNA-containing immune complexes

| PRJNA1014414 | ENA

Global gene expression profile of Japanese encephalitis virus(JEV) infected cytolytic B16F10 and Non-cytolytic JEV resistant B16F10r

Project description:B16F10, a murine melanoma cel line is cytolytic to JEV infection. We have identified a B16F10 cell line variant which is non-cytolytic to JEV infection. This variant cell line has two types of cells, one which is persistently infected JEV and another which is resistant to JEV infection. The JEV-resistant cells (B16F10r) were seperated from the presistently infected cells by single cell cloning. To understand the mechanism of JEV resistance microarray analysis was caried out to Identify and characterize genes differentially expressed during in uninfected/JEV-infected B16F10 and B16F10r cells. Agilent one-color experiment,Organism: Mus musculus ,Agilent Custom Mouse Whole Genome Mouse 8x60k Gene expression designed by Genotypic Technology Private Limited, Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)

2013-08-01 | E-GEOD-42942 | biostudies-arrayexpress

CD160 activation by herpesvirus entry mediator augments inflammatory cytokine production and cytolytic function by NK cells.

Project description:Lymphocyte activation is regulated by costimulatory and inhibitory receptors, of which both B and T lymphocyte attenuator (BTLA) and CD160 engage herpesvirus entry mediator (HVEM). Notably, it remains unclear how HVEM functions with each of its ligands during immune responses. In this study, we show that HVEM specifically activates CD160 on effector NK cells challenged with virus-infected cells. Human CD56(dim) NK cells were costimulated specifically by HVEM but not by other receptors that share the HVEM ligands LIGHT, Lymphotoxin-?, or BTLA. HVEM enhanced human NK cell activation by type I IFN and IL-2, resulting in increased IFN-? and TNF-? secretion, and tumor cell-expressed HVEM activated CD160 in a human NK cell line, causing rapid hyperphosphorylation of serine kinases ERK1/2 and AKT and enhanced cytolysis of target cells. In contrast, HVEM activation of BTLA reduced cytolysis of target cells. Together, our results demonstrate that HVEM functions as a regulator of immune function that activates NK cells via CD160 and limits lymphocyte-induced inflammation via association with BTLA.

| S-EPMC3702646 | biostudies-literature

Cytokine induced NK memory transcriptional profile characterization

Project description:Cytokine induced NK memory transcriptional profile characterization

| PRJNA504634 | ENA