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

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

PROVIDER: PRJNA1082307 | ENA |

REPOSITORIES: ENA

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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

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

| PRJNA1082286 | ENA

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

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 (human)

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

| PRJNA1082305 | ENA

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)

| PRJNA1082304 | ENA

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

Spatially resolved transcriptomic profiling: an experimental comparison of GeoMx Digital Spatial Profiling and Visium CytAssist spatial transcriptomics in three cancer types (GeoMx)

Project description:We performed Visium CytAssist (10X), GeoMx DSP (Nanostring) and Chromium Flex (10X Genomics) full transcriptome profiling on Breast Cancer (BC), Lung Cancer (LC) and diffuse large B cell lymphoma (DLBCL) samples from archival FFPE blocks. We explore the data quality across blocks with different storage times and DV200 values for all the three methods. We compared the cell type signature purity between ST methods Visium and GeoMx by utilising pathology annotations and scRNAseq. For the Visium and Chromium methods with a large number of data points we explored the heterogeneity between tissues. Finally, we demonstrate the discovery of patient-specific tumor-TME interactions across all three methods.

2024-11-01 | E-MTAB-14566 | biostudies-arrayexpress

GeoMX spatial transcriptomic on biphasic Malignant Pleural Mesothelioma

Project description:We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morpho-logical evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler and Cancer Transcriptome Atlas to compare epithelioid and sarcomatoid components transcriptional profile and reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions.

2023-12-07 | E-MTAB-13043 | biostudies-arrayexpress

GeoMx digital spatial profiling on biopsies of triple negative breast cancer patients

Project description:In this study, we analyzed the differential spatial transcriptome of Triple-Negative Breast Cancer (TNBC) patients who responded in an opposite manner to neoadjuvant chemotherapy (NACT): we compared responders displaying pathological complete response (pCR) with no-responders who showed disease progression during therapy. Diagnostic TruCut biopsies were analyzed using the GeoMx Cancer Transcriptome Atlas (Nanostring).

2023-10-12 | E-MTAB-13069 | biostudies-arrayexpress

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