To address these questions, we developed autochthonous mouse models of sporadic MMRd lung and colon cancer via targeted ablation of key genes in the MMR complex, MutL homolog 1 (Mlh1) and MutS homologs 2, 3 and 6 (Msh2, Msh3 and Msh6), and performed preclinical trials to determine ICB sensitivity. The gene discussed is MSH2; the disease is malignant colon neoplasm.