Animal model for antitumor immunity in lung cancer
G12C and G12V mutations are the most predominant forms in KRAS oncogene in lung adenocarcinoma.
Although KRASG12C inhibitors are used in patients with G12C mutation, little is known about the targeted disruption of KRASG12V.
The researchers leveraged the degradation tag (dTAG) system to develop a KRASG12V transgenic mouse model. The authors show that degrading KRASG12V abolishes lung and pancreatic tumors in mice and causes a robust inhibition of KRAS-regulated cancer intrinsic signaling.
The authors also demonstrate that the degradation reprograms the tumor microenvironment towards a stimulatory milieu and drives antitumor immunity, elicited mainly by effector and cytotoxic CD8+ T cells.
https://www.jci.org/articles/view/174249
