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Single-cell RNA sequencing reveals Lin28b-dependent immune modulation in the PDAC tumor microenvironment

GSE306321 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2026/06/21 Platform GPL24247
Summary
Cancer-associated fibroblasts (CAFs) play a crucial role in shaping the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). This study investigates the impact of an RNA-binding protein Lin28b on the immune landscape of PDAC. Single-cell RNA sequencing (scRNA-seq) was performed on orthotopic pancreatic tumors from wild-type (WT) and fibroblast-specific Lin28b knockout (Fsp-Cre;Lin28bfl/fl) mice. Our analysis revealed that Lin28b expression in CAFs promotes an immunosuppressive TME characterized by reduced immune cell infiltration and dampened type I interferon (IFN) signaling. Conversely, Lin28b deletion in CAFs resulted in increased infiltration of immune cells, particularly CD8+ T cells and enhanced cytotoxic T cell activity. These findings identify Lin28b as a CAF-intrinsic molecular brake on anti-tumor immunity and provide a rationale for targeting the Lin28 to overcome PDAC resistance to immunotherapy.
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Direct links to NCBI, no account and no request form: the whole study as GSE306321_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1308258. Searching any of these in the dataset finder brings you back here.

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