Improving CAR T Cell Immunotherapy Response to Diffuse Large B Cell Lymphomas: A Characterization of Metabolic Heterogeneity Across Tumor Models, Tristan Szapary, UG '24 (2278893)
Diffuse Large B Cell Lymphoma (DLBCL) is a prevalent form of blood cancer, with a devasting survival rate of three years. Current treatments begin with aggressive chemotherapy, yet a percentage of DLBCL patients do not show sustained remission or do not qualify for these therapies. A cutting-edge immunotherapy, which are treatments that take advantage of a patient’s own immune system to combat disease, called CAR T Cells has recently proved effective against DLBCL. CAR T Cells are immune cells from a patient’s own body that have been modified to recognize their cancer and eradicate it. However, DLBCL patients are known to heterogeneously respond to the treatment. Studying DLBCL outside of patients employs various tumor lines to model the disease. We asked whether the metabolic heterogeneity of these DLBCL tumor lines impacted how they responded to CAR T Cells. Our results showed that these tumor lines showed variable rates of cell death in response to CAR T Cell treatments. Furthermore, transporters of glucose, glutamine, and arginine–– three different nutrient molecules that are critical for cell survival–– were heterogeneously expressed on the cell surfaces of these tumor lines. These initial findings suggest a potential relationship between the metabolic makeup of a DLBCL tumor and how it responds to the immunotherapy. Future research could experimentally alter these nutrient transporter expressions to see if there is a causal link between metabolism and CAR T Cell efficacy.