Johns Hopkins head and neck endocrine surgeon Richard Alexander Harbison discusses translational research by leveraging clinical specimens to investigate the effect of metabolites in the tumor microenvironment on anti-tumor immunity.
My name is Richard alexander Harbison and I am an otolaryngology, head and neck endocrine surgeon scientist. I'm interested in the effect of tumor metabolism on the immune system's ability to fight cancer. As a surgeon scientist, I'm involved in translational research leveraging clinical specimens from consenting patients to investigate the effect of metabolites in the tumor micro environment on anti tumor immunity, tumor metabolism has been a longstanding area of basic science and clinical interest dating to Otto Warburg's classic observations of increased psychologists in the presence of oxygen. This specialized tumor metabolism provides intermediates required for generating biomass. Recently our collaborators Jonathan, Powell, bob, Leone and barbara Slusher published novel findings identifying divergent metabolic plasticity between cancer versus immune cells. Taking advantage of this finding, the team was able to differentially enhance anti tumor immunity while diminishing tumor cell viability through glutamine antagonism. A number of approaches are currently in clinical trials targeting metabolic pathways to enhance tumor control. One such approach targets mitochondrial metabolism. Recently published preclinical work from our team observed pre treatment efficacy using the mitochondrial complex one inhibitor I A C. S. 01 oh 759. An agent currently in clinical trials, we saw decreased tumor growth in the head and neck cancer. Marine model harboring over expression of the master regulator of the antioxidant response pathway. Nrf two. Another approach we are actively investigating involved strategically targeting nutrient competition between tumor and immune cells. We recently tested metabolic features that diminished anti tumor immunity and highly immune cell infiltrated tumors and identified an association between specific polecat ions and clinical outcomes across a number of tumor types guided by these findings were using state of the art methods, including gene editing, to identify novel clinical targets for enhancing anti tumor immunity by leveraging nutrient competition in the tumor micro environment. And some. There are several ongoing pre clinical and clinical trials testing metabolic therapies to enhance the anti tumor immune response, and we strive to lead the way in this effort for the treatment of head and neck and thyroid cancers.