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Updated: Apr 27, 2026

Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
Published on: August 1, 2025
PARP14 as a master regulator of immune signaling and tumor microenvironment remodeling
Siqi Li1, Xinyue Huang1, Boyan Deng1
1School of Pharmaceutical Sciences, Hebei Medical University, 050017 Shijiazhuang, China.
Abstract:
PARP14 (ARTD8), a unique mono-ADP-ribosyltransferase (mono-ART) in the ADP-ribosyltransferase (ART) superfamily, has emerged as a core regulator of immune signaling and tumor microenvironment (TME), with functions distinct from the canonical DNA repair roles of PARP1/2. This review systematically elucidates the structural basis of PARP14, focusing on its mechanism as a "bimodal transcriptional switch" that enhances signal transducer and activator of transcription (STAT) 6-mediated anti-inflammatory signals while suppressing STAT1-driven interferon responses. We dissect the critical roles of PARP14 in regulating macrophage polarization, lymphocyte fate, and host-virus interactions, revealing how it modulates an immunosuppressive microenvironment and drives metabolic reprogramming. Furthermore, we evaluate the potential of emerging therapeutic strategies, including high-selectivity inhibitors and proteolysis-targeting chimera (PROTAC) degraders, to overcome resistance to immunotherapy. Finally, we highlight that successful clinical translation necessitates resolving tissue-specific paradoxes through targeted delivery and establishing biomarker-based precision stratification systems.
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