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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 (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 (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 (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 (GeoMx)

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 | GSE260598 | GEO

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

2024-03-04 | GSE260597 | GEO

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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

Loss of HLF enables metastasis via cell-collagen interaction in solid cancers

Project description:Metastasis is the main cause of cancer-related deaths, yet the underlying mechanisms remain elusive. Using clear cell renal cell carcinoma (ccRCC), a tumor type with frequent lung metastases, we conducted an in vivo genome-wide CRISPR-Cas9 screen and identified HLF as a potent suppressor of lung metastasis. While HLF translocation is known as an oncogenic event in leukemia, its role in solid cancers remains unclear. Our study revealed that HLF depletion enhanced ccRCC migration and lung metastasis, whereas HLF overexpression abrogated these effects. This finding extended to multiple solid tumor types. In ccRCC patients, HLF expression was reduced at metastatic sites and associated with epigenetic silencing. HLF levels negatively correlated with migration potential in collagen. Mechanistically, HLF regulated leupaxin expression, affecting the integration of collagen stiffness and the actin cytoskeleton through paxillin, thereby repressing cancer cell migration and lung metastasis. These data indicate that HLF influences lung metastasis through cell-collagen interactions in solid tumors.

2025-04-22 | GSE272563 | GEO

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Antitumor Activity of a Novel LAIR1 Antagonist in Combination with Anti-PD1 to Treat Collagen-Rich Solid Tumors.

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). Thus, we hypothesized that LAIR1 and collagen cooperated to suppress therapeutic response. In this study, we report that 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 mAb, elicits myeloid inflammation and allogeneic T-cell responses by binding to LAIR1 and blocking collagen engagement. Furthermore, 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.

| S-EPMC11293989 | biostudies-literature

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