Targeting MDSC and NOX2 in cancer with focus on metastasis

The proposed studies aim to provide insight into the interplay between NOX2+ myeloid derived suppressor cells (MDSC), lymphocyte-mediated immunity, epithelial-to-mesenchymal transition (EMT) and metastasis.

The program addresses two major questions: (1) What is the role of NOX2-derived reactive oxygen species (ROS) for EMT and EMT-related metastasis of epithelial cancer cells? (2) What is the impact of surgery induced NOX2+ MDSC in epithelial cancer, and can MDSC be targeted to reduce the incidence of post-operative metastasis?

We employ state-of-the art methods, including advanced flow cytometry, single cell multiomic profiling of protein and gene expression, and establish clinically relevant animal models of epithelial cancer metastasis.

We also cooperate with clinical units to obtain blood/tumor specimens and perform clinical trials with focus on the impact of MDSC/NOX2-reductive therapy on surgery-induced immunosuppression and post-operative metastasis in pancreatic cancer, which carries distinctly poor prognosis despite surgery with curative intent.

Additionally, we screen and evaluate novel potential NOX2 inhibitors aiming to obtain orally available inhibitors of cancer-related immunosuppression.

Our studies are the first to suggest that inflammation-induced metastasis is driven by NOX2-derived ROS formed by activated MDSC.

Overall, these studies shed light on targetable mechanisms of immunosuppression in cancer that may translate into novel therapies.