Research

IL7R is a bona fide oncogene in the context of lymphoid development. However, despite the evidence suggesting that the pro-tumoral role of IL-7-IL-7R axis extends to non-hematopoietic cancers, there is still no formal evidence that IL7R is an oncogene in solid tumors. Our proposal will:

i) establish whether IL7R is a broader oncogene than initially anticipated;

ii) characterize whether IL-7R is not only a biomarker, but also actually involved in the mechanisms, of resistance to PD-1 axis inhibition;

iii) generate innovative tools to target IL-7R-expression tumor cells and concomitantly potentiate anti-tumor immune responses. The breadth of findings, unique cellular and in vivo models, and novel therapeutic tools with clinical potential that we will generate may extend beyond NCSLC and lung cancer in general, to any IL-7R-expressing tumor, including glioma or breast, bladder, prostate and colorectal cancer, amongst others (reviewed in [7]). If successful, our paradigm-shifting proposal will not only demonstrate that IL7R is an oncogene in solid tumors but also characterize the mechanisms by which a major anti-tumor immune gene is co-opted by cancer cells to benefit tumor progression and treatment resistance. Furthermore, we may ultimately impact clinical practice, introducing a novel biomarker of resistance to PD-1 axis blockade and generating tools to effectively improve treatment outcome in lung cancer and beyond.