Targeting WIP1 reprograms immunosuppressive tumor microenvironment to potentiate immunotherapy response in colorectal cancer - PubMed
7 hours ago
- #immunotherapy
- #colorectal cancer
- #WIP1 inhibition
- WIP1/PPM1D is identified as a critical immunosuppressive driver in colorectal cancer (CRC), with its expression significantly upregulated in tumor tissues.
- Inhibition of WIP1 suppresses tumor growth by remodeling the tumor immune microenvironment, increasing infiltration of anti-tumor macrophages and cytotoxic T cells.
- WIP1 inhibits type I interferon (IFN) signaling by reducing cytoplasmic dsDNA accumulation, inactivating the cGAS-STING-TBK1 axis, and dephosphorylating TBK1 at Ser172.
- Combining a WIP1 inhibitor with a STING agonist synergistically enhances anti-tumor efficacy by amplifying IFNβ production and activating anti-tumor immune response.
- This combination also potentiates anti-PD-1 immunotherapy, offering a strategy to reverse immunotherapy resistance in CRC.
- The study bridges genomic instability with adaptive immune evasion, providing a roadmap for precision immunotherapy in CRC.