Targeting NHEJ activates STING signaling through MYC degradation to boost antitumor immunity in SCLC - PubMed
3 months ago
- #DNAPKcs
- #Immunotherapy
- #SCLC
- SCLC is the most lethal type of lung cancer with a high mutation burden but modest response to immunotherapy.
- SCLC shows the highest expression of NHEJ DNA repair regulator PRKDC (DNAPKcs) among 24 tumor types.
- High PRKDC expression predicts poor response to immunotherapy in SCLC.
- Depletion of DNAPKcs activates the cGAS/STING pathway due to cytoplasmic accumulation of double-stranded DNA, enhancing immunogenicity.
- DNAPKcs depletion leads to proteasomal degradation of MYC via the GSK3β pathway in SCLC cell lines and mouse models.
- DNAPKcs upregulation contributes to immunotherapy resistance, and its inhibition is a promising strategy to boost antitumor immunity in SCLC.