Transcriptional impacts of Myc deficiency in murine bone marrow NK cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE220930 | GEO | 2023/04/19
REPOSITORIES: GEO
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Project description:To understand the mechanism of the defective NK cell functions with MYC deficiency, we isolated splenic NK cells (CD3-NK1.1+CD49b+) from Mycf/f and MycΔ/Δ/Ncr1Cre mice and performed RNA-seq analysis. It revealed that ribosome and natural killer cell-mediated cytotoxicity were the two most enriched pathways in the differentially down-regulated genes. Functional studies showed reduced synthesis of NK cell effector molecules in the NK Cells with MYC deficiency. Collectively, these data suggest impaired ribosomal biogenesis and reduced synthesis of cytotoxic molecule in the NK cells with MYC deficiency.
2021-06-13 | GSE142685 | GEO
Project description:Transcriptional impacts of Myc deficiency in murine bone marrow NK cells
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Project description:Natural killer (NK) cells are innate lymphocytes that play a major role in immunosurveillance against tumor initiation and metastasis spread. Signals and checkpoints that regulate NK cell fitness and function in the tumor microenvironment are not well defined. Transforming grow factor (TGF)- is a recognized suppressor of NK cells that inhibits IL-15 dependent signaling events and induces cellular transdifferentiation, however the role of other SMAD signaling pathways in NK cells is unknown. We used a global, label-free proteomics approach to compare the protein expression profiles of NK cells in the presence of TGF-b or activin-A.
2020-04-06 | PXD011672 | Pride
Project description:Transcriptome of mouse splenic NK cells with MYC deficiency
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Project description:Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) induced by natural killer (NK) cells is one important mechanism by which cetuximab exerts its anti-tumoral effect. Therefore, molecular characterization of NK cells subpopulations may identify predictive biomarkers of cetuximab efficacy in mCRC patients and would provide novel therapeutic targets to enhance cetuximab-mediated ADCC.
2025-05-23 | PXD057989 | Pride
Project description:Background: T cell-based immunotherapies including immune checkpoint blockade (ICB) and chimeric antigen receptor (CAR) T cells can induce durable responses in cancer patients. However, clinical efficacy is limited due to the ability of cancer cells to evade immune surveillance. While T cells have been the primary focus of immunotherapy, recent research has highlighted the importance of Natural Killer (NK) cells in directly recognizing and eliminating tumor cells and playing a key role in the set-up of an effective adaptive immune response. The remarkable potential of NK cells for cancer immunotherapy is demonstrated by their ability to broadly identify stressed cells, irrespective of the presence of neoantigens, and their ability to fight tumors that have lost their Major Histocompatibility Complex class I (MHC I) expression due to acquired resistance mechanisms.
However, like T cells, NK cells can become dysfunctional within the tumor microenvironment. Strategies to enhance and reinvigorate NK cell activity hold potential for bolstering cancer immunotherapy.
Method: In this study, we conducted a high-throughput screen to identify molecules that could enhance primary human NK cell function. After compound validation, we investigated the effect of the top performing compound on dysfunctional NK cells that were generated by a newly developed in vitro platform. Functional activity of NK cells was investigated utilizing compounds alone and in combination with checkpoint inhibitor blockade. The findings were validated on patient-derived intratumoral dysfunctional NK cells from different cancer types.
Results: The screening approach led to the identification of a Cbl-b inhibitor enhancing the activity of primary human NK cells. Furthermore, the Cbl-b inhibitor was able to reinvigorate the activity of in vitro generated and patient-derived dysfunctional NK cells. Finally, Cbl-b inhibition combined with TIGIT blockade further increased the cytotoxic potential and reinvigoration of both in vitro generated and patient-derived intratumoral dysfunctional NK cells.
Conclusion: These findings underscore the relevance of Cbl-b inhibition in overcoming NK cells dysfunctionality with the potential to complement existing immunotherapies and improve outcomes for cancer patients.
2024-08-12 | MSV000095572 | MassIVE
Project description:Natural killer (NK) cells can be grouped into distinct subsets that are localized to different organs and exhibit different capacity to secrete cytokines and mediate cytotoxicity. Despite these hallmarks that reflect tissue-specific specialization in NK cells, little is known about the factors that control the development of these distinct subsets. The basic leucine zipper transcription factor nuclear factor interleukin 3 (Nfil3; E4bp4) is essential for bone marrow-derived NK cell development but it is not clear whether Nfil3 is equally important for all NK cell subsets nor how it induces NK lineage commitment. Here we show that Nfil3 is required for the formation of Eomesodermin (Eomes)-expressing NK cells, including conventional medullary and thymic NK cells, whereas TRAIL+ Eomes- NK cells develop independent of Nfil3. Loss of Nfil3 during the development of bone marrow-derived NK cells resulted in reduced expression of Eomes and, conversely, restoration of Eomes expression in Nfil3-/- progenitors rescued NK cell development and maturation. Collectively, these findings demonstrate that Nfil3 drives the formation of mature NK cell by inducing Eomes expression and reveal the differential requirements of NK cell subsets for Nfil3. RNA-sequencing of natural killer (NK) cell subsets
2014-05-07 | E-GEOD-54291 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukemia (B-CLL) and small lymphocytic lymphoma (SLL) are part of the same disease classification but are defined by differential distribution of tumor cells. B-CLL is characterized by significant immune suppression and dysregulation but this is nottypical of patients with SLL. Natural killer cells (NK) are important mediators of immune function but have been relatively poorly studied in patients with B-CLL/SLL.
2016-09-30 | E-MTAB-4403 | biostudies-arrayexpress
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
Project description:In mouse models, the bromodomain PHD finger transcription factor (BPTF) chromatin remodeling subunit in tumor cells suppresses natural killer (NK) cell antitumor activity. In vitro, BPTF suppresses NK cell cytolytic activity to mouse and human cancer cell lines, demonstrating a conserved function.
2017-04-28 | GSE85756 | GEO