Event details

Please note this event begins at 1pm and ends at 2pm.

The Ludwig Princeton Distinguished Lectureship features world class cancer researchers.

Jeff Rathmell, leading cancer immunologist from Vanderbilt University, will present his talk "Metabolic Control of Immunotherapy and Inflammation."

T cells in tumors and other inflamed tissues accumulate signs of stress and mitochondrial damage that affect cell metabolism but remain poorly understood. The metabolism of T cells and other immune cells is dynamically regulated and influences biosynthesis, signaling, and cell fate. We have shown that CD4 T cell subsets are metabolically distinct and that each requires a specific metabolic program for their function. Immune cells do not act in isolation, however, and are subject to systems and microenvironmental factors that shape their metabolism and function. On a systemic level, obesity leads to a state of chronic inflammation and is a risk factor for cancer incidence and progression. However, cancer immunotherapy can be enhanced in obesity in the cancer-obesity paradox. We have shown that induction of the immune checkpoint molecule PD-1 on tumor associated macrophages contributes to this paradox and immunotherapy responses in obese individuals. At a microenvironmental level, tissue temperature changes with body location, fever, and inflammation. We tested the effects of elevated temperatures found that T cells broadly become more pro-inflammatory but a subset of CD4 T cells, Th1 cells, selectively experience mitochondrial stress that activates a heat-sensitive molecular circuit to shape T cell fate. The metabolic interaction of immune cells with their environment can both drive disease and offer new therapeutic opportunities.