The Trustees of the University of Pennsylvania, doing business as Clinical Practices of the University of Pennsylvania, received a $483,706 Project Grant from the National Cancer Institute (CFDA 93.396 Cancer Biology Research program) to conduct fundamental research on the regulation of tumor-associated immune macrophages (TAMs) and their role in cancer development and immunotherapy response.
The research aims to elucidate how the composition and activity of the mitochondrial electron transport chain complex IV in TAMs is controlled by the induction of the proteins NDUFA4L3 and miR-147 in response to interferons. This metabolic regulation is hypothesized to be a key factor in determining the anti-tumor or pro-tumor functions of TAMs within the tumor microenvironment. The project will leverage advanced techniques such as single-cell transcriptomics, spatial analysis, metabolomics, and high-resolution structural modeling to delineate the underlying mechanisms. The findings could inform the development of novel cancer immunotherapeutic strategies.