Gene expression anaylsis of tumor stimulated human NK cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE55977 | GEO | 2014/03/18
SECONDARY ACCESSION(S): PRJNA241495
REPOSITORIES: GEO
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Project description:Genome wide expression profiling of human NK cells stimulated with K562 erythroleukemic tumor cells after four hours of NK-tumor co-culture. Responding NK cells were compared to non-responding NK cells, delineated by display of CD107 on the NK cell surface following cytotoxic granule release. We hypothesized that tumor responses would initiate rapid changes in gene expression in the NK cell that would identify new features of the anti-tumor response of NK cells. Results identify NK cell activation responses and induction of TNF superfamily molecules with immunoregulatory activity. Human peripheral blood NK cells were co-cultured with tumor target cell line K562 for 4 hours with GolgiStop (brefeldin) then stained for granule exocytosis marker CD107a / CD107b, and NK cell markers then FACS sorted for responding NK cells (CD107+) and non-responding NK cells (CD107-). Pooled donor sample comprised NK cells from 3 individuals.
2014-03-18 | E-GEOD-55977 | biostudies-arrayexpress
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2018-11-30 | GSE116660 | GEO
Project description:Constitutively found at high frequencies, the role for NK cell proliferation remains unclear. Here, a shift in NK cell function from predominantly producing interferon-? (IFN-?), a cytokine with proinflammatory and antimicrobial functions, to producing the immunoregulatory cytokine IL-10, is defined during extended murine cytomegalovirus infection. The NK cells driven to express IL-10 in vivo acquired responsiveness to IL-12 and IL-21 for IL-10 production, but neither cytokine was required for the endogenous response. In vitro studies with IL-2 to support proliferation and in vivo adoptive transfers into murine cytomegalovirus-infected mice demonstrated that NK cell proliferation and further division enhanced the change. During infection, the responding NK cells acquired histone modifications indicative of an open IL-10 gene, and an IL-10 response was proliferation dependent ex vivo if the NK cells had not yet expanded in vivo but independent if they had. Thus, a novel role for proliferation in supporting changing innate cell function is discovered. The chromatin status of ex vivo isolated NK cells during MCMV infection was investigated by ChIP-seq on histone epigenetic marks (H3K4m3, H3K27m3, H3K36m3) on day 0, day 1.5 and day 3.5 post infection.
2014-08-05 | E-GEOD-55834 | biostudies-arrayexpress
Project description:A better understanding of innate responses induced by vaccination is critical for designing optimal vaccines. Here, we studied the diversity and dynamics of the NK cell compartment after prime-boost immunization with the modified vaccinia virus Ankara using cynomolgus macaques as a model. Mass cytometry was used to deeply characterize blood NK cells. The NK cell subphenotype composition was modified by the prime. Certain phenotypic changes induced by the prime were maintained over time and, as a result, the NK cell composition prior to boost differed from that before prime. The key phenotypic signature that distinguished NK cells responding to the boost from those responding to the prime included stronger expression of several cytotoxic, homing, and adhesion molecules, suggesting that NK cells at recall were functionally distinct. Our data reveal potential priming or imprinting of NK cells after the first vaccine injection. This study provides novel insights into prime-boost vaccination protocols that could be used to optimize future vaccines.
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Project description:Natural killer (NK) cells are crucial regulators of antiviral and anti-tumor immune responses. Although in humans some NK cell transcriptional programs are relatively well established, NK cell transcriptional networks in non-human primates (NHP) remain poorly delineated. Here we performed RNA-Seq experiments using purified NK cells from experimentally naïve rhesus macaques, providing the first transcriptional characterization of pure NK cells in a NHP species. This novel NK cell transcriptomic signature (NK RMtsig) overlaps with published human NK signatures, allowing us to identify new key signaling and transcription factor networks underlying NK cell function. Finally, we show that applying NK RMtsig to an unrelated rhesus macaque cohort infected with SIVmac251 or ZIKV can sensitively detect NK cell repertoire perturbations, thus confirming applicability of this approach. In sum, we propose this NHP NK cell signature will serve as a useful resource for future studies involving infection, disease or treatment modalities in NHP
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Project description:Constitutively found at high frequencies, the role for NK cell proliferation remains unclear. Here, a shift in NK cell function from predominantly producing interferon-γ (IFN-γ), a cytokine with proinflammatory and antimicrobial functions, to producing the immunoregulatory cytokine IL-10, is defined during extended murine cytomegalovirus infection. The NK cells driven to express IL-10 in vivo acquired responsiveness to IL-12 and IL-21 for IL-10 production, but neither cytokine was required for the endogenous response. In vitro studies with IL-2 to support proliferation and in vivo adoptive transfers into murine cytomegalovirus-infected mice demonstrated that NK cell proliferation and further division enhanced the change. During infection, the responding NK cells acquired histone modifications indicative of an open IL-10 gene, and an IL-10 response was proliferation dependent ex vivo if the NK cells had not yet expanded in vivo but independent if they had. Thus, a novel role for proliferation in supporting changing innate cell function is discovered.
2014-08-05 | GSE55834 | GEO
Project description:Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity and play a critical role in mediating cellular immunity in advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested a novel recombinant adenovirus-transduced autologous DC-based vaccine that simultaneously induces T cell responses against three melanoma-associated antigens for advanced melanoma patients. We examined the impact of this vaccine on the NK cell profile in melanoma patients. Relative immune cell population abundance was evaluated as previously described (Danaher et al. JITC, 2017). The abundance of the CD56dim NK cell gene signature was compared between pattients with better and worse outcome.
2019-01-03 | GSE124574 | GEO
Project description:Natural killer (NK) cells can be divided into phenotypic subsets based on the expression of receptors that bind self-MHC-I molecules with differing affinities; a concept termed licensing or education. Here we show that NK cell subsets exhibit markedly different migratory, effector, and immunoregulatory functions on dendritic cells and antigen-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells preferentially trafficked to draining lymph nodes and produced GM-CSF, which promoted the expansion and activation of dendritic cells, and ultimately resulted in sustained antigen-specific CD8+ T cell responses. In contrast, licensed NK cells preferentially migrated to infected parenchymal tissues and produced greater levels of interferon-γ (IFN-γ). Importantly, human NK cell subsets exhibited similar phenotypic characteristics and patterns of cytokine production. Collectively, our studies demonstrate a critical demarcation between the functions of licensed and unlicensed NK cell subsets, with the former functioning as the classical effector subset in inflamed tissues and the latter as modulators of adaptive immunity helping to prime immune responses in draining lymph nodes.
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Project description:T cells play a critical role in the immune system by recognizing and responding to foreign and tumor antigens. Dysregulation or dysfunction of T cells can lead to autoimmune diseases, infectious diseases and cancer. Understanding the mechanisms that regulate T cell immunity is therefore critical for the development of effective therapies for diseases associated with T cell dysfunction. Co-inhibitory ‘checkpoint molecules’ such as programmed cell death protein 1 (PD-1) are tightly connected to T cell activation and balance excessive or prolonged immune activation by T cell-intrinsic signaling. Here, by screening for mediators of NK cell recognition on T cells, we identify the Ig superfamily ligand B7H6 to be highly expressed by activated T cells, including patient-infused CD19-targeting chimeric antigen receptor (CAR)-T cells. We show that, unlike other checkpoint molecules, B7H6 mediates NKp30-dependent recognition and subsequent cytolysis of activated T cells by NK cells. B7H6+ T cells are prevalent in the tissue and blood of several diseases, and we find that their abundance in tumor tissue positively correlates with clinical response in a cohort of immune checkpoint inhibitor-treated patients with esophageal cancer. In humanized mouse models, we demonstrate that NK cell surveillance via B7H6 is relevant in limiting the persistence and anti-tumor activity of CAR T cells in vivo and that its genetic depletion enhances T cell proliferation and persistence. In summary, we provide evidence of B7H6 protein expression by activated T cells and suggest the B7H6-NKp30 axis as therapeutically actionable NK cell-dependent immune checkpoint that regulates human T cell function.
2024-01-12 | GSE253152 | GEO
Project description:The Ig superfamily ligand B7H6 subjects T cell responses to NK cell surveillance
| PRJNA1064123 | ENA