Uncovering metabolic mechanisms for tumor-driven immunosuppression with mass spectrometry imaging

Scientists have uncovered ways to turn the body’s natural immune system against cancer – an approach termed immunotherapy. While highly effective for some patients and cancer types, many patients do not respond. This creates a fundamental knowledge gap: why do only certain patients respond to immunotherapies? The answer may lie in the adage – “you are what you eat”. Cancers, at the cellular level, consume lots of fats, sugars, and 1000’s of other molecules collectively termed ‘the metabolome’. This leads to immune cells needing to fight for key fuels, and tumor cell production of toxic by-products which can kill natural immune cells. Together, this can incapacitate the immune system and may be why immunotherapies fail. Resolving this metabolic hurdle will require emerging, state-of-the-art technologies that can distinguish cancer cell metabolism and immune cell metabolism as they exist in the tissue (i.e. with their spatial distribution preserved). This project aims to develop and apply cutting-edge technologies to profile tumors which are responsive & unresponsive to immunotherapy, providing a fundamental understanding of tumor metabolism and allowing us to identify new opportunities to improve targeted immunotherapy treatments.