Inhibition of MAPK p38α overcomes the cancer immunosurveillance defect caused by FPR1 loss-of-function mutation - PubMed
5 hours ago
- #FPR1 mutation
- #MAPK p38α
- #cancer immunotherapy
- A loss-of-function polymorphism in human FPR1 leads to compromised dendritic cell (DC) migration and weakened immunosurveillance, triggering early epithelial cancers.
- A mouse model with a human-mimetic FPR1 mutation replicates the DC defect seen in Fpr1 knockout animals.
- Inhibitors of MAPK p38α were found to correct the FPR1 defect in type 1 conventional DCs (cDC1).
- MAPK p38α inhibitors restore the function of FPR1 knockout or mutated cDC1 in vitro and in vivo, improving responses to anticancer therapies.
- Pharmacological inhibition of MAPK p38α normalizes accelerated colorectal carcinogenesis in mice with FPR1-related immune system defects.