Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MiR-155 Regulates AML Tumor-Specific mRNA Vaccine Responses

ABSTRACT: Acute myeloid leukemia (AML) is a malignant clonal expansion of myeloid stem and progenitor cells, impeding normal hematopoiesis and culminating in bone marrow failure and mortality. Treatment with cytotoxic chemotherapy is often initially successful, but the development of chemo-resistant disease is common, indicating that new treatments are still needed. Recently, messenger RNA (mRNA) vaccines have emerged as potent inducers of antitumor immunity against solid tumors, yet their utility in the setting of AML, and the molecular mechanisms that govern their activity, are poorly defined. In our study, we demonstrate that microRNA-155 (miR-155) function in T cells is vital both for anti-tumor immunity against AML and mRNA vaccine efficacy against AML. Loss of miR-155 in both CD4+ and CD8+ T cells in conditional knockout mice (miR-155 fl/fl CD4+Cre) resulted in deficient antitumor immunity against syngeneic ovalbumin-expressing C1498 murine AML (C1498-OVA). Further, sterilizing immunity was provided by a tumor antigen-specific mRNA vaccine against C1498-OVA AML, but only if T cell-expressed miR-155 was present, in a process that included the differentiation of KLRG1+ CD8+ T cells. Single-cell RNA sequencing revealed distinct, miR-155-dependent transcriptome regulation of mRNA vaccine-responsive CD8+ T cells, which included a subset of genes that are regulated by miR-155 only during the mRNA vaccine response, indicating a novel context specific role for miR-155. These data indicate that T cell expressed miR-155 governs responses to tumor-specific mRNA vaccines by facilitating activation and differentiation cascades in CD8+ T cells and expanding memory CD8+ T cell reservoirs.

ORGANISM(S): Mus musculus

PROVIDER: GSE310056 | GEO | 2026/07/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Sequencing of tumor associated (B16f10-OVA) mir-155 Wt or deficient CD4+ and CD8+ T cells

Project description:Tumor associated CD4+ and CD8+ T cells were sorted from B16f10 OVA expressing tumors in miR-155 flox, miR-155 flox CD4Cre+, and miR-155 flox CD4Cre+ mice treated with immune checkpoint blocking (ICB) antibodies by flow sorting on CD45+CD3+CD4+ cells and CD45+ CD3+CD8+ cells. RNA was collected from these cells to perform RNA sequencing of total RNA.

2017-09-11 | GSE101690 | GEO

Context- and cell-type specific function of miR155-Socs1 interaction in immune regulation

Project description:The microRNA (miRNA) dependent regulation of gene expression confers robustness to cellular phenotypes and controls responses to extracellular stimuli. Although a single miRNA can regulate expression of hundreds of target genes, it is unclear whether any of its distinct biological functions can be due to the regulation of a single target. To explore in vivo the function of a single miRNA-mRNA interaction, we mutated the 3' UTR of a major miR-155 target SOCS1 to specifically disrupt its regulation by miR-155. We found that under physiologic conditions and during autoimmune inflammation or viral infection some immunological functions of miR-155 were fully or largely attributable to the regulation of SOCS1, whereas others could be accounted only partially or not at all by this interaction. Our data suggest that the role of a single miRNA-mRNA interaction is cell type- and biological context-dependent. Naive WT, SOCS1KI and miR-155KO OVA-specific OT-1 TCR transgenic CD8+ T cells (1x10e4 per mouse) were adoptively transferred into CD45.1+ wt mice prior to infection with MCMV-OVA. WT, SOCS1KI and miR-155KO NK cells (2x10e5 per mouse) were adoptively transferred into CD45.1+ Klra8KO (Ly49H-deficient) mice prior to infection with MCMV. On d4 post infection, CD45.2+ CD44+ CD8+ OT-1 and CD45.2+ Ly49H+ NK1.1+ CD3- NK cells were FACS-sorted (BD FACS ARIA2). Each condition has 3 sequencing replicates.

2015-05-10 | E-GEOD-68511 | biostudies-arrayexpress

A microRNA-regulated transcriptional state defines intratumoral CD8+T cells that respond to immunotherapy

Project description:Rising rates of advanced-stage colorectal cancer (CRC) and poor survival rates necessitate effective therapeutic options. Immune checkpoint inhibition (ICI), specifically anti-PD-1 therapy, shows potential, but clinical determinants of a positive response are suboptimal. Here, we identify microRNA-155 (miR-155) as necessary for CD8 T cell infiltrated tumors through an unbiased in vivo Crispr-Cas9 screen of tumor-antigen-specific CD8 T cell-related miRNAs. MiR-155 was necessary for a vital CD8 T cell differentiation cascade by repressing Ship-1, thereby inhibiting stemness and Tcf-1 while enhancing effector function and Cxcr6 expression, an indispensable aspect of anti-tumor and -PD-1 responses. Through a miR-155-dependent CD8 T cell transcriptional profile, we identified a gene signature that predicts anti-PD-1 responses across ten cancers. Taken together, our findings support a model whereby miR-155 serves as a central axis for CD8 T cell-dependent immunity in CRC and anti-PD-1 responses against multiple cancers that may be leveraged therapeutically or as a biomarker.

2025-02-10 | GSE262873 | GEO

miR-155 enhances PRC2 activity via polycomb-like protein Phf19 to sustain T cell antitumor immunity [ChIP-Seq]

Project description:The microRNA miR-155 is essential for CD8+ T cell antiviral and antitumor immunity but the mechanisms behind its activity remain unresolved. Here, we show that miR-155 increased CD8+ T cell antitumor function by restraining T cell senescence and functional exhaustion through epigenetic silencing of key drivers of effector differentiation. miR-155 enhanced the function of polycomb repressor complex 2 (PRC2) indirectly by promoting the expression of the PRC2 cofactor Phf19 via AKT signaling. Phf19 orchestrated a transcriptional program extensively shared with miR-155 to enhance T cell engraftment, polyfunctionality, and antitumor immunity. These effects were dependent on the histone-binding capacity of Phf19 which is critical for the PRC2 recruitment to chromatin. These findings establish miR-155–Phf19–PRC2 as a pivotal axis regulating CD8+ T cell differentiation. Targeting the microRNA–polycomb-group protein circuitry is a promising route to potentiate cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate.

2019-03-11 | GSE99918 | GEO

miR-155 enhances PRC2 activity via polycomb-like protein Phf19 to sustain T cell antitumor immunity [RNA-Seq]

2019-03-08 | GSE99801 | GEO

Adenovirus Serotype 5 Vectors Trigger IL-27-Dependent Inhibitory CD4+ T Cell Responses

Project description:Viral vectors are attractive vaccine platforms that elicit robust innate and adaptive immune responses; however, viral vector vaccine candidates vary greatly in their ability to induce protective immunity. Ad5 vectors elicit robust CD8+ T cell responses but typically characterized by an exhausted phenotype. The mechanisms by which Ad5 vectors induce dysfunctional CD8+ T cells have not been fully elucidated. Here we demonstrate that Ad5 vectors, but not Ad26 vectors, elicit exhausted antigen-specific IL-10+PD1+ CD4+ T cells with a dysfunctional transcriptional profile, and these cells effectively suppress CD8+ T cells responses in vivo. Induction of inhibitory CD4+ T cells by Ad5 vectors was associated with increased IL-27 expression, and IL-27 blockade improved CD4+ T cell polyfunctionality. Together our data highlight a novel role for IL-27 in regulating responses to viral vector vaccines. Splenic CD45.2+ OT-II TCR-Tg CD4 T cells from CD45.1+ B6 mice immunized with Ad5-OVA or Ad26-OVA were purified by FACS on day 10 post-immunization

2016-06-01 | E-GEOD-73118 | biostudies-arrayexpress

MicroRNA-155 is upregulated in Hoxa9/Meis1 leukemia inducing cells but is dispensable for in vivo transformation and leukemia development

Project description:OBJECTIVE: The microRNA miR-155 is upregulated in Hoxa9 and Meis1 leukemia inducing cells (LIC) , and miR-155 accelerates the onset of acute myeloid leukemia (AML) together with Hoxa9 but through largely unknown molecular mechanisms. The impact of miR-155 on accelerated onset of leukemia in the context of Hoxa9 and Meis1 is also unclear. To further resolve this, we performed a gene expression profiling, in the context of Hoxa9 and Meis1 leukemogenesis with miR-155 knocked out. RESULTS: Gene expression profiling of Hoxa9/Meis1 LIC without miR-155 does not delay the onset of AML and the gene expression changes are small

2017-04-27 | GSE80660 | GEO

Expression profile of wild type (WT) vs miR-155-/- in FLT3-ITD+ AML (MV4-11) cell lines

Project description:The expression profile in miR-155-/- FLT3-ITD+ AML is unknown. Using empty vector (EV) or two distinct miR-155 (S3 or S10) lentiviral CRISPR-Cas9 infected FLT3-ITD+ AML cell lines (MV4-11 cells), we performed next generation RNA sequencing to determine the expression profile in these cells dependent on miR-155. We found a number of pathways dysregulated, including STAT5 activation.

2016-07-01 | GSE71541 | GEO

Gene profile of Wt and miR-155-/- Tfh cells

Project description:Differential gene expression profile of Tfh and non-Tfh cells from both Wt and miR-155-/- mice spleens. Wt and miR-155-/- mice were immunized with OVA. 8 days post immunization, CD4+CXCR+PD1+ Tfh cells and CD4+CXCR5-PD1- non Tfh cells were sorted from mice spleens for analyses.

2014-12-09 | E-GEOD-58371 | biostudies-arrayexpress

Expression profile of wild type (WT) vs miR-155-/- in FLT3-ITD+ AML (MV4-11) cell lines

2016-07-01 | E-GEOD-71541 | biostudies-arrayexpress