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Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors

ABSTRACT: Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors

PROVIDER: PRJNA1082286 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28167404_1.fastq.gz	Fastqsanger.gz
	SRR28167404_2.fastq.gz	Fastqsanger.gz
	SRR28167405_1.fastq.gz	Fastqsanger.gz
	SRR28167405_2.fastq.gz	Fastqsanger.gz
	SRR28167106.fastq.gz	Fastqsanger.gz

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Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors (GeoMx)

Project description:Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors (GeoMx)

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Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors (mouse)

Project description:Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors (mouse)

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Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors (human)

Project description:Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors (human)

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Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors (human)

Project description:We recently reported that resistance to PD-1-blockade in a refractory lung cancer-derived model involved increased collagen deposition and the collagen-binding inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), and thus we hypothesized that LAIR1 and collagen cooperated to suppress therapeutic response. Here, we report LAIR1 is associated with tumor stroma and is highly expressed by intratumoral myeloid cells in both human tumors and mouse models of cancer. Stroma-associated myeloid cells exhibit a suppressive phenotype and correlate with LAIR1 expression in human cancer. NGM438, a novel humanized LAIR1 antagonist monoclonal antibody, elicits myeloid inflammation and allogeneic T cell responses by binding to LAIR1 and blocking collagen engagement. Further, a mouse-reactive NGM438 surrogate antibody sensitized refractory KP mouse lung tumors to anti-PD-1 therapy and resulted in increased intratumoral CD8+ T cell content and inflammatory gene expression. These data place LAIR1 at the intersection of stroma and suppressive myeloid cells and support the notion that blockade of the LAIR1/collagen axis can potentially address resistance to checkpoint inhibitor therapy in the clinic.

2024-03-04 | GSE260597 | GEO

Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors (mouse)

2024-03-04 | GSE260596 | GEO

Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors (GeoMx)

2024-03-04 | GSE260598 | GEO

Anti-tumor activity of a novelLAIR1antagonist in combination with anti-PD-1to treat collagen-rich solid tumors

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-03-04 | GSE260599 | GEO

Effect of anti-mouse TNF and IL-6 antibodies as well as their combination in a collagen-induced arthritis mouse model

Project description:Additive effects of anti-TNF and anti-IL-6 were evaluated in a murine collagen-induced arthritis (CIA) model by RNA-seq

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Targeting the HSP47-Collagen Axis Inhibits Brain Metastasis by Reversing M2 Microglial Polarization and Restoring Anti-Tumor Immunity

Project description:Brain metastases (BrMs) are the leading cause of death in patients with solid cancers. BrMs exhibit a highly immunosuppressive milieu and poor response to immunotherapies; however, the underlying mechanism remains largely unclear. Here, we show that upregulation of HSP47 in tumor cells drives metastatic colonization and outgrowth in brain by creating an immunosuppressive microenvironment. HSP47-mediated collagen deposition in the metastatic niche promotes microglial polarization to M2 phenotype via the α2β1 integrin/NF-κB pathway, which upregulates the anti-inflammatory cytokines and represses CD8+ T cell anti-tumor responses. Depletion of microglia reverses HSP47-induced inactivation of CD8+ T cells and abolishes brain metastasis. Col003, an inhibitor disrupting HSP47-collagen association restores an anti-tumor immunity and enhances the efficacy of anti-PD-L1 immunotherapy in BrMs-bearing mice. Our study supports that HSP47 is a critical determinant of M2 microglial polarization and immunosuppression, and blocking the HSP47-collagen axis represents a promising therapeutic strategy against brain metastatic tumors.

2024-03-22 | GSE261941 | GEO

Fibroblast pyruvate carboxylase is required for collagen production in the tumor microenvironment

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