New immunocompetent model breakthrough accelerates immunotherapy research for lung cancer

Three MELIS-UPF PIs developed a novel immunocompetent mouse model of mismatch repair-deficient (dMMR) lung adenocarcinoma (LUAD) by selectively ablating the Mlh1 gene to better evaluate immune checkpoint inhibitors. The study reveals that anatomical tumor location fundamentally influences treatment outcomes; while subcutaneous tumors showed only partial sensitivity to anti-PD1 therapy, orthotopic lung tumors exhibited a robust therapeutic response with a substantial reduction in tumor burden and enhanced immune infiltration of memory CD4+ cells. By demonstrating how the specific organ microenvironment dictates immunogenicity, this pioneering platform bridges a critical translational gap, offering a highly accurate preclinical toolkit to predict clinical responses and overcome resistance to immunotherapies in lung cancer patients.

Reference:
Zadra I, Abad E, Krasko A, Cerdán Porqueras V, Subirana-Granés M, Reyes D, Borredat P, Pasquali L, Aramburu J, López-Rodriguez C, Janic A (2025). A novel mismatch repair deficient lung adenocarcinoma model for immunotherapy research. Cancer Letters, 629, 217882. DOI: 10.1016/j.canlet.2025.217882