Collectively, these data demonstrate that in the LSL-K-ras<sup>G12D</sup> murine lung cancer model, inflammatory macrophage-Th17 cell axis is critical to tumorigenesis and that IL-10 blocks this process primarily via a direct effect on the former.
We translated our findings to two murine models of lung cancer, including orthotopic human xenograft and Kras<sup>LSL/G12D</sup> mouse models of lung cancer.
In comparison, MALT1 deficiency does not affect tumor progression in a mouse model (LSL-K-ras(G12D); CCSP-Cre; Malt1(-/-)) in which lung cancer is induced by expressing a K-ras mutant.
Co-administration of BI-2536 and fasudil either in the LSL-KRAS(G12D) mouse model or in a patient tumour explant mouse model of KRAS-mutant lung cancer suppresses tumour growth and significantly prolongs mouse survival, suggesting a strong synergy in vivo and a potential avenue for therapeutic treatment of KRAS-mutant cancers.
The therapeutic potential of microRNAs for preventing and treating lung cancer using the Kras(LSL-G12D/+);p53(LSL-R172H/+)mouse model suggests that miR-34 may be useful in sensitizing tumors to other conventional therapeutics.
Using an inducible LSL-KRAS(G12D) model of lung cancer in vivo, we show a transient upregulation of Notch pathway activity in early tumor precursor lesions.