ArticlebioRxiv : the preprint server for biology2024
Key Regulatory Elements of the TGFβ-LRRC15 Axis Predict Disease Progression and Immunotherapy Resistance Across Cancer Types.
Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Transforming growth factor-beta (TGFβ) has dual roles in cancer, initially suppressing tumors but later promoting metastasis and immune evasion. Efforts to inhibit TGFβ have been largely unsuccessful due to significant toxicity and indiscriminate immunosuppression. Leucine-rich repeat-containing protein 15 (LRRC15) is a TGFβ-regulated antigen expressed by mesenchymal-derived cancer cells and cancer-associated fibroblasts (CAFs). In preclinical studies, ablation of TGFβ-driven LRRC15+ CAFs increased tumor infiltration of CD8+ T cells. However, the underlying pathobiological mechanisms prompting TGFβ's upregulation of LRRC15 expression are unclear. Using an integrated approach combining functional compound screening with single-cell RNA sequencing, we reveal key genomic features regulating TGFβ's ability to increase LRRC15 expression on cancer cells. Construction of gene regulatory networks converged our analyses on four key genes-
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