LIF-responsive genes in tumor-associated myeloid cells from ascitic fluid of syngeneic ovarian cancer model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE79852 | GEO | 2019/04/23
REPOSITORIES: GEO
Similar Datasets
Project description:LIF has an important role in immunosupression in different scenarios, such as in embryo implantation in the uterus, autoimmune disease or organ transplantation. In tumor progression it has been largely demonstrated the importance of immune system. The fact that LIF is highly expressed in certain tumor types, in addition to its immunomodulatory properties, led us to hypothesize that tumors expressing high levels of LIF might be promoting an immune-tolerant microenvironment precluding the anti-tumor immune response. To establish whether the effect of LIF was relevant in the context of human monocytes, we isolated CD14+ cells (monocytes) from peripheral blood mononuclear cells (PBMCs) from healthy donors and analyzed the effect of LIF blockade. Instead of using recombinant LIF, we studied the effect of the endogenous LIF secreted by U251 cell line. RNA was extracted from the CD14+ cells and the transcriptomic analysis was performed.
2022-02-01 | GSE79851 | GEO
Project description:Leukemia Inhibitory Factor (LIF) plays an essential role in the maintenance of pluripotency of mouse embryonic stem cells (mESCs). LIF withdrawal induces mESC differentiation. To define noval pluripotent factors downstream of LIF signaling, cDNA microarray was used and seveal well-known pluripotent genes were found to respond to LIF withdrawal, including Klf4, Esrrb, Tbx3, and Prdm14.
2015-06-23 | GSE70104 | GEO
Project description:Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Tumor cell lysis by CTLs was attenuated when PD-L1 on tumor cells was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. Gene expression profile of mouse CTLs caused by PD-L1-overexpressing ovarian cancer was related to human CTLs exhaustion. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination. Genome-wide transcriptional changes in OT-1 mouse CD8+ T cells that were co-incubated with OVA peptide-loaded ID8 mouse ovarian cancer cell lines. CTLs from 4 mice were devided into 2 groups, and co-incubated with PD-L1-overexpressed ID8 or PD-L1-depleted ID8.
2012-07-09 | E-GEOD-39205 | biostudies-arrayexpress
Project description:In order to identify the genes involved in LIF/gp130 self-renewal response, we analyzed the transcriptome of Gs2 ES cells induced to differentiate upon LIF withdrawal for 16h, 24h and 48h (LIF16, LIF24 and LIF48 respectively)and compared them to that of undifferentiated ES Gs2 cells continuously maintained in the presence of LIF. Since this cell line also carry a tetracycline regulatable dominant negative form of Stat3 (Stat3F, all the experiment was done in the presence of Tetracycline (tet ON) to avoid Stat3F expression. Keywords: time-course
2004-07-01 | GSE1150 | GEO
Project description:Leukemia inhibitory factor (LIF) is an important endogenous factor for photoreceptor protection. Lif is known to be upregulated both in induced and inherited disease models of photoreceptor degeneration only in a subset of Muller cells. Since Lif is induced in Muller cells in response to photoreceptor injury, we studied its regulation in Muller cells. We have recently identified several AU-rich elements (AREs) within the 3′ untranslated region (UTR) of Lif . We also showed that as a result of these elements Lif encodes a highly unstable mRNA. mRNAs containing AREs in the 3`UTR undergo rapid ARE-mediated mRNA decay in the cytoplasm which is mediated by the RNA–binding proteins. In order to identify the RNA-binding proteins that are involved in the regulation of Lif transcripts, we will use the biotin-labelled RNA. By using this methodology, we will isolate the related RNA binding proteins. We plan to analyze the isolated proteins by mass spectrometry, and compare the mass spectrometry results of different regions with or without AREs . Once we identify the specific proteins that bind only to AREs, we will do the functional characterization of these proteins by cotransfecting the constructs with AREs and the siRNA that inhibits the expression of related RNA binding protein.
2016-07-20 | PXD001463 | Pride
Project description:Migration and homing of immune cells are critical for immune surveillance. Efficient trafficking is mediated by cellular expression of combinations of adhesion and chemokine receptors which guide immune cells, in response to chemokine signals, to specific locations within tissues and the lymphatic system. This supports tissue-localized immune reactions and systemic immunity. However, fundamental questions remain as to how these signals are initiated and regulated. Here we show that disruption of leukaemia inhibitory factor (LIF) production from group 2 innate lymphoid cells (ILC2s) prevents immune cells from leaving the lungs and migrating to the lymph nodes. During pulmonary viral infection this dysregulation leads to plasmacytoid dendritic cells becoming retained in the lungs where they improve tissue-localized anti-viral immunity. By comparison, during chronic allergen challenge the accumulation of immune cells in the lung leads to the pronounced formation of tertiary lymphoid structures in the lung, and a failure to seed the lymph nodes. Mechanistically, ILC2-derived LIF induces the production of the chemokine CCL21 from lymphatic endothelial cells lining the pulmonary lymphatic vessels, thereby licencing the homing of CCR7+ immune cells to lymph nodes. Thus, ILC2-derived LIF production dictates the egress of immune cells from the lungs regulating tissue versus systemic immunity and the balance between allergen and viral responsiveness in the lungs.
2024-07-30 | GSE243691 | GEO
Project description:We report that ES cells cultured in ground state (2i and 2i/LIF) culture conditions are heterogeneous and show heterogeneus expression of extraembryonic markers. Using a highly sensitive reporter for the endoderm marker Hex we can sort Hex high and low populations from either serum/LIF or 2i/LIF and demonstrate that they have different functional properties. Here we explored the transcriptional basis of these functional differences and noted that Hex low (HV-) and Hex high (HV+) populations showed more distinct expression profiles in 2i/LIF than in serum/LIF. Additionally in 2i/LIF the HV+ population showed an upregulation of extraembryonic markers (such as trophoblast stem cell specific genes) and also imprinted genes compared to the HV- population, which is not observed when these populations are sorted from serum/LIF. We also analysed the transcriptional effect of LIF in 2i by analysing unsorted ES cells cultured in either 2i alone or 2i with LIF. We observed that the addition of LIF led to an upregulation of extraembryonic markers but did not effect the expression of pluripotency genes, other than Klf4. Additionally, the most significantly upregulated genes from 2i/LIF cultured ES cells compared to 2i cultured ES cells showed the greatest correlation to placental tissue when compared to the GNF tissue specific expression database. This analysis, alongside functional experiments, suggested that HV+ ES cells in 2i/LIF corresponded to an extraembryonically primed population of cells and that the addition of LIF supported this population.
2013-06-11 | GSE45182 | GEO
Project description:Active suppression of tumor-specific T lymphocytes can limit the immune-surveillance and immunotherapy efficacy. While tumor-recruited CD11b+ myeloid cells are known mediators of tumor-associated immune dysfunction, the true nature of these suppressive cells and the fine biochemical pathways governing their immunosuppressive activity remain elusive. Here we describe a population of circulating CD11b+/IL-4Rα+, inflammatory-type monocytes that is elicited by growing tumors and activated by IFN-γ released from T lymphocytes. CD11b+/IL-4Rα+ cells produce IL-13 and IFN-γ and integrate the downstream signals of these cytokines to trigger the molecular pathways suppressing antigen-activated CD8+ T lymphocytes. Analogous immunosuppressive circuits are active in CD11b+ cells present within the tumor microenvironment. These suppressor cells challenge the current idea that tumor-conditioned immunosuppressive monocytes/macrophages are alternatively activated. Moreover, our data show how the inflammatory response elicited by tumors has detrimental effects on the adaptive immune system and suggest novel approaches for the treatment of tumorinduced immune dysfunctions. Experiment Overall Design: Labeled cRNA extracted from a a total of 9 samples was hybridized to the Affymetrix GeneChip MG-U74Av2 which contains 12,488 probe sets . The 3 control samples represented 3 replicates of RNA extracted from Cd11b cells purified from the spleen of tumor-free mice. The 6 samples obtained from tumor-bearing mice represented 3 replicates each of RNA extracted from Cd11b cells purified from the spleen of tumor-bearing mice. Three out of six samples were incubated for 24 hours in complete medium.
2009-04-29 | E-GEOD-5455 | biostudies-arrayexpress
Project description:Myeloid derived suppressor cells (MDSCs) markedly expand and participate in the suppression of immune responses in inflammation and tumor microenvironment. It was confirmed that MDSCs could be generated in vitro from bone marrow cells (BMCs) after 4 days GM-CSF only or GM-CSF plus IL-6 treatment. To identify the regulation of MDSCs in tumor microenvironment, we analyzed the gene expression from tumor cell ID8 supernant-induced MDSCs compared to BMCs.
2016-12-13 | GSE92303 | GEO
Project description:Active suppression of tumor-specific T lymphocytes can limit the immune-surveillance and immunotherapy efficacy. While tumor-recruited CD11b+ myeloid cells are known mediators of tumor-associated immune dysfunction, the true nature of these suppressive cells and the fine biochemical pathways governing their immunosuppressive activity remain elusive. Here we describe a population of circulating CD11b+/IL-4Rα+, inflammatory-type monocytes that is elicited by growing tumors and activated by IFN-γ released from T lymphocytes. CD11b+/IL-4Rα+ cells produce IL-13 and IFN-γ and integrate the downstream signals of these cytokines to trigger the molecular pathways suppressing antigen-activated CD8+ T lymphocytes. Analogous immunosuppressive circuits are active in CD11b+ cells present within the tumor microenvironment. These suppressor cells challenge the current idea that tumor-conditioned immunosuppressive monocytes/macrophages are alternatively activated. Moreover, our data show how the inflammatory response elicited by tumors has detrimental effects on the adaptive immune system and suggest novel approaches for the treatment of tumorinduced immune dysfunctions. Keywords: Analysis of Cd11b cells from tumor-free and tumor-bearing mice
2006-10-06 | GSE5455 | GEO