Ontology highlight
ABSTRACT:
PROVIDER: PRJNA687237 | ENA |
REPOSITORIES: ENA
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Project description:BACH2 restricts NK cell maturation and function limiting immunity to cancer metastasis
| PRJNA883986 | ENA
Project description:The liver has an exceptional capacity for regeneration which is crucial for maintaining liver function. Since transcriptional regulation of genes controlling metabolism and cell division is a hallmark of liver regeneration (LR), we investigated the role of Zinc-finger and homeboxes 2 (ZHX2), a transcription factor critical for regulating liver postnatal gene expression and hepatic lipid hemostasis, in LR. Our results show that hepatocyte-specific Zhx2 knockout (Zhx2-KOhep) enhances LR after 2/3 partial hepatectomy in mice. Proteomics assays revealed higher mitochondrial oxidative phosphorylation (OXPHOS) in Zhx2-KOhep mouse livers. Oxygen consumption rate (OCR) and ATP generation assays confirmed the enhanced OXPHOS in Zhx2-KOhep mouse livers and human hepatocytes with ZHX2 knockdown.
2023-10-17 | PXD027897 | Pride
Project description:The characteristics of the tumor immunosuppressive microenvironment represent a major challenge limiting the efficacy of immunotherapy. Our previous results suggested that cryo-thermal therapy (CTT), a tumor ablation system developed in our laboratory, could promote macrophage M1-type polarization and full maturation of DCs to remodel the immunosuppressive environment. However, it is not clear which cells respond promptly to CTT. CTT can cause extensive cell death and the release of danger-associated molecular patterns (DAMPs) and antigens. Neutrophils are the first white blood cells recruited to sites of damage and acute inflammation. We therefore hypothesized that neutrophils were the initial cells to respond to CTT and were involved in the subsequent establishment of antitumor immunity. We found that CTT led to a rapid and strong proinflammatory neutrophil response, which was essential for the long-term survival of mice. In vivo neutrophil depletion and in vitro coculture experiments demonstrated that CTT-induced neutrophils promoted the differentiation of monocytes toward to mature antigen presenting cells and further upregulated the expression of IFN-γ and cytotoxic molecules in T and NK cells in a CD86-dependent manner. These results reveal the important role of neutrophil-monocyte interactions for the development of anti-tumor immunity and highlight that CTT could be used as an immunotherapy for targeting neutrophils and monocytes to enhance antitumor immunity.
2024-03-02 | GSE259010 | GEO
Project description:N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification on RNA. NK cells are the predominant innate lymphoid cells that mediate anti-viral and anti-tumor immunity. However, whether and how m6A modifications affect NK cell immunity remains unknown. Here, we discover that YTHDF2, a well-known m6A reader, is upregulated in NK cells upon activation by cytokines, tumors, and cytomegalovirus infection. Ythdf2 deficiency in NK cells impairs NK cell anti-tumor and anti-viral activity in vivo. YTHDF2 maintains NK cell homeostasis and terminal maturation, correlating with modulating NK cell trafficking and regulating Eomes, respectively. YTHDF2 promotes NK cell effector function and is required for IL-15-mediated NK cell survival and proliferation by forming a STAT5-YTHDF2 positive feedback loop. Transcriptome-wide screening identifies Tardbp to be involved in cell proliferation or survival as a YTHDF2-binding target in NK cells. Collectively, we elucidate the biological roles of m6A modifications in NK cells and highlight a new direction to harness NK cell anti-tumor immunity.
2021-05-08 | GSE174027 | GEO
Project description:BPTF Depletion Enhances NK Cell Mediated Antitumor Immunity
| PRJNA339273 | ENA
Project description:Innate lymphoid cells (ILCs) are a heterogeneous population of lymphocytes that coordinate early immune responses and maintain tissue homeostasis. Type 1 immune responses are mediated by natural killer (NK) cells and group 1 ILCs (ILC1s). Despite their shared features, NK cells and ILC1s display profound differences among various tissue microenvironments. Here, we identify the inositol polyphosphatase INPP4B as a hallmark feature of tissue-resident ILC1s and intratumoral NK cells using a scRNA-seq atlas of tissue-associated and circulating NK/ILC1s. Conditional deletion of Inpp4b in ILC1s and NK cells reveals that it is necessary for the homeostasis of tissue-resident ILC1s but not circulating NK cells at steady-state. Inpp4b-deficient cells display increased rates of apoptosis and reduced activation of the pro-survival molecule AKT. Furthermore, expression of Inpp4b by NK/ILC1s is necessary for their presence in the intratumoral environment and lack of Inpp4b impairs antitumor immunity. These findings highlight INPP4B as a novel regulator of tissue residency and antitumor function in ILC1s and NK cells.
2024-01-01 | GSE250334 | GEO
Project description:Natural killer (NK) cells play pivotal roles in antitumor immunity, yet their connection to tumor metabolism remains unclear. Our systematic analysis of multiomics data and survival data from colorectal cancer (CRC) patients uncovered a novel association between mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) and NK cell infiltration that influences disease progression. ACAT1, a metabolic enzyme involved in reversible conversion of acetoacetyl-CoA to two molecules of acetyl-CoA, exhibits nuclear protein acetylation activity through its translocation. Under immune stimulation, mitochondrial ACAT1 can be phosphorylated at serine 60 (S60) and enters the nucleus; however, this process is hindered in nutrient-poor tumor microenvironments. Nuclear ACAT1 directly acetylates lysine 146 of p50 (NFKB1), attenuating its DNA binding and transcriptional repression activity and thereby increasing the expression of immune-related factors, which in turn promotes NK cell recruitment and activation to suppress colorectal cancer growth. Furthermore, significant associations were found among low nuclear ACAT1 levels, decreased S60 phosphorylation, and reduced NK cell infiltration, as well as poor prognosis in CRC. Our findings reveal an unexpected function of ACAT1 as a nuclear acetyltransferase and elucidate its role in NK cell-dependent antitumor immunity through p50 acetylation.
2025-03-17 | GSE291785 | GEO
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