Postdoctoral Research Fellow Vanderbilt University Medical Center, United States
Background: Renal Cell Carcinoma (RCC) is a highly metastatic, complex range of tumors. Currently, there is limited knowledge to guide treatment and the available treatments have only been exhaustively studied in the most common forms of RCC. While primary tumor can be resected, systemic treatments, unfortunately, only have robust responses in small cohorts of patients. In an effort to improve RCC therapy, immunotherapies have been developed to target crosstalk between immune cells and cancer cells by inhibiting immune cell checkpoint and signaling pathways within the RCC tumor microenvironment (TME). However, these immunotherapies are then applied broadly regardless of the type of kidney cancer.
Methods: We propose an experimental approach to identify metabolic targets for RCC therapeutics by capitalizing on the heterogeneity of the TME to elucidate the metabolic landscape of the RCC TME and reveal common fundamental features of host immune response. Using an unselected cohort of RCC patient tumor types, we will separate tumor and immune cell populations and perform a multi-omic approach to map the metabolism of these cell populations within the TME of RCC patient tumors. We will pair this data with imaging mass spectrometry and multiplex immunofluorescent imaging to determine the spatial metabolic environment of the TME by visualizing the distribution of metabolites and metabolic proteins.
Results: Using these methods and an unselected cohort of RCC tumors, we will be able to identify putative inhibitors and validate the physiological viability of these metabolic programs as metabolic therapeutic targets for a diverse range of RCC tumors.
Conclusions: As a result, we will be able to expand our knowledge of the immune cells that comprise the TME as a feature of RCC tumors and identify new RCC therapeutic targets to extend immune treatments that would reduce the burden of disease in a larger, more diverse patient cohort than the current treatments allow.
