Deciphering Glioma Microenvironment Entry Mechanisms of Myeloid-Derived Suppressor Cells
While immunotherapy has shown to be effective in treating some cancer types, the highly immunosuppressive tumor microenvironment of glioblastoma (GBM) provides unique challenges. As an example, immune checkpoint inhibitors, such as for the programmed-death-1 (PD-L1/PD-1) pathway, have had promising pre-clinical outcomes but failed to show efficacy in phase III clinical trials. One potential explanation is the infiltration of the tumor microenvironment by immune-suppressive cells such as myeloid-derived suppressor cells (MDSCs). Encouragingly, in experimental studies where MDSCs are targeted by drugs in combination with PD-1 blockade in mice, median survival increased. We develop an ODE model of the interactions between cancer cells, T cells, and MDSCs specific to the glioma microenvironment. We then optimize administration of combination immunotherapy with the overall objective being minimization of the tumor burden and MDSC entry as well as maximization of survival time.