MAIT cells regulate NK cell mediated tumor immunity (RNA-Seq)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA742401 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14987551.fastq.gz | Fastqsanger.gz | |||
| SRR14987553.fastq.gz | Fastqsanger.gz | |||
| SRR14987555.fastq.gz | Fastqsanger.gz | |||
| SRR14987557.fastq.gz | Fastqsanger.gz | |||
| SRR14987559.fastq.gz | Fastqsanger.gz |
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Project description:This study reveals the dichotomous role of MAIT cells in regulating NK cell mediated anti-tumor immunity.
2021-07-06 | GSE179140 | GEO
Project description:MAIT cells regulate NK cell mediated tumor immunity (NanoString)
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Project description:This study reveals the dichotomous role of MAIT cells in regulating NK cell mediated anti-tumor immunity.
2021-07-06 | GSE179139 | GEO
Project description:The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-γ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment.
| S-EPMC8346465 | biostudies-literature
Project description:The tumor microenvironment (TME) harbors numerous types of cellular stress that can activate Heat Shock Factor 1 (HSF1), a central regulator of stress response. HSF1 has been shown to directly regulate diverse gene programs beyond the classical heat shock response in a cell-type- and context-specific manner. Here, we uncover significant variability in HSF1 levels and activity between immune populations in patient tumors, with the lowest in natural killer (NK) cells. We demonstrate that accumulation of activated HSF1 in the TME dampens anti-tumor immunity through impairing NK cell cytotoxicity, which could be rescued by NK cells with homeostatic levels of HSF1. HSF1 stabilization results in altered chromatin accessibility and expression of surface receptors and signaling proteins involved in NK cell activation. We further reveal direct occupancy of HSF1 at promoters of genes encoding mediators of NK cell cytotoxicity. Single-cell transcriptional profiling of the TME in the context of elevated HSF1 revealed an inverse relationship between the stress response status and NK cell effector function. Collectively, this work identifies a novel role of HSF1 in regulating the NK cell activation state and subsequent anti-tumor functionality.
2022-01-26 | GSE194364 | 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:To elucidate the mechanisms that regulate metabolic suppression versus sustained metabolic fitness in NK cells in the tumor microenvironment (TME), we assessed global differences in protein levels via proteomics in NK cells exposed to the TME or control media.
2021-04-12 | PXD016996 | Pride
Project description:To show the similarity among MAIT-iPSCs, hiPSCs and hESCs and the gradual change of global gene expression of reMAIT cells along with differentiation, this experiment was designed. MAIT cells, MAIT-iPSCs, hiPSCs, hESCs, MAIT cells, and reMAIT cells at the several differerent stages of differentiation were collected. Then, they were applied in this experiment.
2013-03-21 | E-GEOD-44559 | biostudies-arrayexpress
Project description:Antibodies targeting “immune checkpoints” have revolutionized cancer therapy by reactivating tumor-resident cytotoxic lymphocytes, primarily CD8 T cells. Interest in targeting analogous pathways in other cytotoxic lymphocytes is growing. Natural killer (NK) cells are key to cancer immunosurveillance by eradicating metastases and driving solid tumor inflammation. NK cell anti-tumor function is dependent on the cytokine interleukin (IL)-15. Ablation of the IL-15 signaling inhibitor CIS (Cish) enhances NK cell anti-tumor immunity by increasing NK cell metabolism and persistence within the tumor microenvironment (TME). The TME has also been shown to impair NK cell fitness via the production of immunosuppressive TGF-b, a suppression which occurs even in the presence of high IL-15 signaling. Here, we identified an unexpected interaction between CIS and the TGF-b signaling pathway in NK cells. Independently, Cish- and Tgfbr2- deficient NK cells are both hyper-responsive to IL-15 and hypo-responsive to TGF-b, with dramatically enhanced anti-tumor immunity. Remarkably, when both these immunosuppressive genes are simultaneously deleted in NK cells, mice are largely resistant to tumor development, suggesting that combining suppression of these two pathways might represent a novel therapeutic strategy to enhance innate anti-cancer immunity.
2022-04-11 | GSE200134 | GEO
Project description:MICA and MICB (MICA/B) are expressed by many human cancers due to cellular stress and tag cells for elimination by cytotoxic lymphocytes through NKG2D receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA/B proteins. We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA/B by human cancer cells. These antibodies inhibited tumor growth in multiple fully immuno-competent mouse models and also reduced human melanoma metastases in a humanized mouse model. Anti-tumor immunity was mediated mainly by NK cells through activation of NKG2D and CD16 Fc receptors. This novel approach prevents the loss of important immunostimulatory ligands by human cancers and reactivates antitumor immunity.
2018-02-01 | GSE109542 | GEO