P286R : Tumor susceptibility and immune response in mouse models

Heterozygous knock-in Pole^P286R/+ mice develop numerous early-onset cancers of diverse lineages. Conditional expression of the Pole^P286R/+ allele in endometrium elicits endometrial cancers with high mutational burden and robust antitumor immune responses. The Pole^P286R/+ variant also enhances antitumor immunity and response to immune checkpoint blockade in a syngeneic mouse model.

References

Li, H.D. et al. Polymerase-mediated ultramutagenesis in mice produces diverse cancers with high mutational load. J Clin Invest 128, 4179-4191 (2018). https://pubmed.ncbi.nlm.nih.gov/30124468/
Li, H.D. et al. A Pole^P286R/+mouse model of endometrial cancer recapitulates high mutational burden and immunotherapy response. JCI Insight 5, e138829 (2020). https://pubmed.ncbi.nlm.nih.gov/32699191/
Ma, X. et al. Functional landscapes of POLE and POLD1 mutations in checkpoint blockade-dependent antitumor immunity. Nat. Genet. 54, 996-1012 (2022). https://pubmed.ncbi.nlm.nih.gov/35817971/