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Evaluation of potential impact of anti-LIF therapy on the tumor microenvironment in the immune-component mice by scRNA-seq analysis.

ABSTRACT: We report the application of single-molecule-based sequencing technology for anti-LIF therapy on the tumor microenvironment in the immune-component mice.C57 mice were treated with isotype control IgG, anti-LIF, anti-PD-1, or the combination of anti-LIF with anti-PD-1 (combo) individually after subcutaneously injected with PAN02 cells for 5 days. we explored the therapeutic potentials in blocking the LIF-LIFR signaling pathway and confirmed that it can effectively enhance the tumor responsiveness to PD-1 immunotherapy by shifting the T-cells population composition in addition to the inhibition of tumor growth.

ORGANISM(S): Mus musculus

PROVIDER: GSE193121 | GEO | 2024/12/31

REPOSITORIES: GEO

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Oncostatin M (OSM) and Leukemia Inhibitory factor (LIF) treatment of osteoblasts via LIF and OSM receptors

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2016-08-17 | GSE83418 | GEO

Epithelial LIF signaling limits apoptosis and lung injury during bacterial pneumonia

Project description:During bacterial pneumonia, alveolar epithelial cells are critical for maintaining gas exchange and providing antimicrobial as well as pro-immune properties. We previously demonstrated that leukemia inhibitory factor (LIF), an IL-6 family cytokine, is produced by type II alveolar epithelial cells (ATII) and is critical for tissue protection during bacterial pneumonia. However, the target cells and mechanisms of LIF-mediated protection remain unknown. Here, we demonstrate that antibody-induced LIF blockade remodels the lung epithelial transcriptome in association with increased apoptosis. Based on these data, we performed pneumonia studies using a novel mouse model in which LIFR (the unique receptor for LIF) is absent in lung epithelium. While LIFR was detected on the surface of epithelial cells, its absence only minimally contributed to tissue protection during pneumonia. Single-cell RNA-sequencing (scRNAseq) was conducted to identify adult murine lung cell types most prominently expressing LIFR, revealing endothelial cells, mesenchymal cells, and ATIIs as major sources of LIFR. Sequencing data indicated that ATII cells were significantly impacted as a result of pneumonia, with additional differences observed in response to LIF neutralization, including but not limited to gene programs related to cell death, injury, and inflammation. Overall, our data suggest that LIF signaling on epithelial cells alters responses in this cell type during pneumonia. However, our results also suggest separate and perhaps more prominent roles of LIFR in other cell types, such as endothelial cells or mesenchymal cells, which provide grounds for future investigation.

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Super-enhancer driven LIF/LIFR-STAT3-SOX2 regulatory feedback loop promotes cancer stemness in head and neck squamous cell carcinoma (ChIP-seq)

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Super-enhancer driven LIF/LIFR-STAT3-SOX2 regulatory feedback loop promotes cancer stemness in head and neck squamous cell carcinoma (ATAC-seq)

2024-11-06 | GSE274994 | GEO

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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.

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Project description:LIF has an important role in immunosupression in different scenarios, such as embryo implantation in the uterus, autoimmune disease or organ transplantation. We decided to study the role of LIF on the immune response to cancer. We found that tumors expressing high levels of LIF promote an immune-tolerant microenvironment precluding the anti-tumor immune response. To establish the effect of LIF on tumor-associated myeloid cells (TAMCs), we used a syngeneic ovarian tumor model (ID8 cell line). We treated animals bearing tumors with anti-LIF antibody and isolated myeloid (CD11b+) cells from the ascites. RNA was extracted from the CD11b+ cells and the transcriptomic analysis was performed.

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Project description:Pharmacological inhibition of LIFR impairs ovarian cancer progression by blocking LIF/LIFR autocrine loop

| PRJNA992123 | ENA

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Identification of a LIF-responsive replication-competent human β cell

Project description:The beta (β) cell mass formed during embryogenesis is amplified by cell replication that occurs primarily during fetal and early postnatal development. Thereafter, β cells become functionally mature and their mass is maintained by a very low rate of replication. For those few β cells that replicate in adult life, it is not known how replication is initiated, uncoupled from β cell function nor whether this occurs in a specialized subset of β cells. To explore these issues with the aim of controlling replication of mature human β cells, we capitalized on a YAP overexpression system that induces cell cycle re-entry in stem cell derived-β cells. Singe cell RNA sequencing revealed an upregulation of components of the leukemia inhibitory factor (LIF) pathway upon cell cycle re-entry. Experimental activation of the LIF pathway induces replication and expansion of human stem cell derived- and adult β cells in vitro and in vivo. In both stem cell derived- and adult human β cells, the expression of the LIF receptor LIFR is restricted to a subset of β cells with distinct transcriptional profiles and defines a subpopulation of β cells with increased replication rates. Further analysis identified 15 transcription factors whose gene networks are active in replicating β cells. Overall, this study sheds light on regulatory networks that control β cell replication and reveals a heterogeneity in LIF responsiveness and replication competence.

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