Leila Akkari Group
Immune cells and macrophages in therapeutically challenging tumors
Tumor initiation, progression and response to therapy rely on more than genomic alterations, and cancers evolve within a complex tissue microenvironment. Thus, to impact therapeutic outcome, our understanding of cancer dynamics and diversity must not solely view cancer cells as the fundamental unit, but as part of an integrated and reactive system centered around heterotypic communication with their environment.
Our laboratory focuses on the role of a major population of immune cells, macrophages, in therapeutically challenging tumors, to identify vulnerabilities in cancer cell/ stroma heterotypic communication that can be targeted therapeutically. We study the microenvironment-mediated mechanisms of tumor maintenance, therapeutic resistance and recurrence in brain and liver malignancies. In particular, we investigate the acquired resistance mechanisms resulting from dynamic alterations in the activation and recruitment of macrophages and their mediators in response to standard of care treatment. We generate and utilize cancer mouse models of glioma and hepatocellular carcinoma combined with immune cell lineage tracing system to unravel the functions of resident and infiltrating macrophages in sheltering tumor cells during cytotoxic therapy response. Our approach is to trace these immune cells at different stages of tumor progression and response to therapy, to unravel potential vulnerabilities that we can then exploit in combinatorial anti-cancer treatments.