Article
Loss of p53 and mutational heterogeneity drives immune resistance in an autochthonous mouse lung cancer model with high tumor mutational burden.
Cancer cell - 9 Oct 2023
Zhu Mingrui, Kim Jiwoong, Deng Qing, Ricciuti Biagio, Alessi Joao V, Eglenen-Polat Buse, Bender Matthew E, Huang Hai-Cheng, Kowash Ryan R, Cuevas Ileana, Bennett Zachary T, Gao Jinming, Minna John D, Castrillon Diego H, Awad Mark M, Xu Lin, Akbay Esra A
Abstract excerpt
The role of tumor mutational burden (TMB) in shaping tumor immunity is a key question that has not been addressable using genetically engineered mouse models (GEMMs) of lung cancer. To induce TMB in lung GEMMs, we expressed an ultra-mutator variant of DNA polymerase-E (POLE)P286R in lung epithelial cells. Introduction of PoleP286R allele into KrasG12D and KrasG12D; p53L/L (KP) models significantly increase their...
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