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Series GSE217847 Query DataSets for GSE217847
Status Public on Sep 07, 2023
Title IL-1b+ tumor-associated macrophages fuel pathogenic inflammation in pancreatic cancer
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Other
Summary Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with high resistance to therapies. Inflammatory and immunomodulatory signals co-exist in the pancreatic tumor microenvironment (TME), leading to dysregulated repair and cytotoxic responses. Tumor-associated macrophages (TAMs) are key players in PDAC, but their diversity prevented therapeutic exploitation. Here, we combined single-cell and spatial genomics with functional experiments to elucidate macrophage functions in pancreatic cancer. We uncovered an inflammatory loop between tumor cells and interleukin (IL)-1B+ TAMs, a subset of macrophages elicited by a local synergy between prostaglandin E2 (PGE2) and tumor necrosis factor (TNF)-A. Physical proximity with IL-1B+ TAMs was associated with inflammatory reprogramming and acquisition of pathogenic properties by a subset of PDAC cells. This occurrence was an early event in pancreatic tumorigenesis and led to persistent transcriptional changes associated with disease progression and poor patient outcome. Blocking PGE2 or IL-1B elicited TAM reprogramming and antagonized tumor cell-intrinsic and -extrinsic inflammation, leading to PDAC control in vivo. Targeting the PGE2-IL-1B axis may enable preventive or therapeutic strategy to reprogramming of immune dynamics in pancreatic cancer.
 
Overall design Refer to individual Series
 
Citation(s) 37914939
Submission date Nov 12, 2022
Last update date Nov 10, 2023
Contact name Renato Ostuni
Organization name San Raffaele Telethon Institute for Gene Therapy
Street address Via Olgettina 58
City Milano
ZIP/Postal code 20132
Country Italy
 
Platforms (3)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
GPL33597 Resolve Biosciences Molecular Cartography custom platform (98 genes)
Samples (136)
GSM6727498 BMDM PGE2 stimulation 1 hour RNA-seq replicate 1
GSM6727499 BMDM PGE2 stimulation 1 hour RNA-seq replicate 2
GSM6727500 BMDM PGE2 stimulation 1 hour RNA-seq replicate 3
This SuperSeries is composed of the following SubSeries:
GSE217842 IL-1b+ tumor-associated macrophages fuel pathogenic inflammation in pancreatic cancer - Bulk RNA-seq
GSE217843 IL-1b+ tumor-associated macrophages fuel pathogenic inflammation in pancreatic cancer - Spatial transcriptomics of mouse PDAC samples
GSE217845 IL-1b+ tumor-associated macrophages fuel pathogenic inflammation in pancreatic cancer - scRNAseq of human PDAC samples
Relations
BioProject PRJNA901006

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Supplementary file Size Download File type/resource
GSE217847_RAW.tar 9.2 Gb (http)(custom) TAR (of CSV, JPG, JSON, MTX, PNG, TIFF, TSV, TXT)
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