Genomic approaches to studying tumor-microenvironment interactions

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Todd Golub, Director and a founding core member of the Broad Institute of MIT and Harvard.

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Genomic approaches to the study of cancer have proven powerful for the discovery of tumor cell autonomous mechanisms of tumor pathogenesis and therapeutic strategies. Less obvious, however, is how to take similarly systematic approaches to the study of tumor-microenvironment interactions that historically have been studied using hypothesis-driven approaches. I will discuss recent work in our laboratory attempting to extend genomic approaches to more complex systems. Specifically, I will describe our use of spatial transcriptomics to discover microenvironment-derived survival factors in Hodgkin lymphoma, yielding candidate therapeutic approaches that are immediately testable in clinical trials. In addition, I will describe our effort to use genome-wide functional genomic approaches to discover targets in AML cells that induce AML phagocytosis by co-cultured macrophages, thereby identifying new macrophage inhibitory checkpoints.