ArticleCell death and differentiation2026
Targeting WIP1 reprograms immunosuppressive tumor microenvironment to potentiate immunotherapy response in colorectal cancer.
Article in Cell death and differentiation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Mechanisms and Emerging Strategies to Overcome Immunotherapy Resistance in Cold Tumours of Colorectal Cancer.OncoTargets and therapy · 2026Review
- p53 Pathway-Targeted Therapeutic Strategies in Glioblastoma: A CNS-Specific Framework Integrating Therapeutic Resistance, Molecular Stratification, CNS Pharmacology, and Clinical Translation.Drug design, development and therapy · 2026Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
While immunotherapy based on immune checkpoint inhibitors (ICIs) shows limited efficacy in colorectal cancer (CRC) due to its immunosuppressive tumor microenvironment, strategies to activate innate immunity remain underexplored. Here, we identified wild-type p53-induced phosphatase 1 (WIP1/PPM1D) as a critical immunosuppressive driver in CRC, with its expression significantly upregulated in tumor tissues. Genetic or pharmacological inhibition of WIP1 robustly suppressed tumor growth by remodeling the tumor immune microenvironment, marked by increased infiltration of anti-tumor macrophages and cytotoxic T cells. Mechanistically, WIP1 inhibited type I interferon (IFN) signaling by reducing cytoplasmic dsDNA accumulation to inactivate the cGAS-STING-TBK1 axis, and by directly dephosphorylating TBK1 at Ser172 to suppress its kinase activity. Strikingly, combining a WIP1 inhibitor with a STING agonist synergistically enhanced anti-tumor efficacy by amplifying IFNβ production to activate anti-tumor immune response. This combination further potentiated anti-PD-1 immunotherapy. In summary, this study uncovers WIP1 as a pioneering dual-functional suppressor of tumor-intrinsic STING activation and establishes a rationally designed "STING-WIP1 co-targeting" strategy to reverse immunotherapy resistance. Our findings bridge genomic instability with adaptive immune evasion, offering a roadmap for precision immunotherapy in CRC.
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Registered trials
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