This study aimed to characterize the tumor-infiltrating immune cells population in Kras/tumor protein 53 (Trp53)-driven lung tumors and to evaluate the combinatorial antitumor effect with MEK inhibitor (MEKi), trametinib, and immunomodulatory monoclonal antibodies (mAbs) targeting either programmed death -1 (PD-1) or programmed cell death ligand 1 (PD-L1) in vivo.
Interestingly, p53 co-mutation rendered KRAS<sup>G12C</sup> lung tumors less sensitive to combination treatment with selumetinib and chemotherapy.<b>Conclusions:</b> Our data demonstrate that unique <i>KRAS</i> mutations and concurrent mutations in tumor-suppressor genes are important factors for lung tumor responses to MEK inhibitor.
The ability of these signatures to stratify samples according to functional activation of MEK and/or selumetinib sensitivity was shown in multiple independent melanoma, colon, breast, and lung tumor cell lines and in xenograft models.