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Arginine deprivation reshapes tumor and immune transcriptional programs and potentiates IFNγ–JAK–STAT signaling in 4T1 murine breast tumors

GSE310301 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2026/01/14 Platform GPL24247
Summary
Arginine availability is a key metabolic regulator of tumor and immune cell function. We performed single-cell RNA sequencing of orthotopic 4T1 murine triple-negative breast tumors to define cell type–specific transcriptional adaptations to arginine deprivation. We demonstrate that arginine depletion induces widespread transcriptional reprogramming across both stromal and immune compartments, with particularly pronounced effects in cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). In tumor cells, cancer cell–intrinsic (via Ass1 knockdown), systemic (via an arginine-free diet), or combined restriction of arginine availability resulted in elevated inflammatory responses, including activation of interferon-alpha (IFNα) and interferon-gamma (IFNγ) signaling, and, to a lesser extent, IL6–JAK–STAT3 signaling. These changes, mediated by tumor microenvironment (TME)–supportive interactions, sustain tumor cell survival under arginine-deprived conditions.
Published in
Inhibition of Tumor Microenvironment-Driven JAK-STAT Signaling Enhances Response to Arginine Deprivation Therapy in Triple-Negative Breast Cancer
Tishler H, Ziman S, Cheng K et al. · Cells 2025 · PMID 41511309 · doi:10.3390/cells15010025
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Also filed as BioProject PRJNA1365725 and SRA study SRP646044. Searching any of these in the dataset finder brings you back here.

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