Lay summary
Immunotherapy (checkpoint blockade) is a promising new treatment option for cancer that is curative in some cases. Unfortunately, cures are only seen in the minority of patients, pointing to underlying mechanisms of resistance that need to be characterised and targeted. Even a robust anti-tumour immune response must overcome antagonism within the tumour microenvironment, much of which is orchestrated by low oxygen (hypoxia), attracting and educating a variety of immunosuppressive cells populations that reduce activated T cell functions. We will test the hypothesis that hypoxia targeted agents that eradicate the viable hypoxic tumour cell compartment, can silence multiple immunosuppressive mechanisms in a coordinated fashion and thus improve the outcome of immunotherapy. We will test the hypothesis that hypoxia is a targetable mechanism of tumour microenvironment induced immune suppression and that eliminating the immune privilege afforded by tumour hypoxia is a clinically feasible opportunity.