MEK Inhibition May Prevent the Recruitment of NK Cells in the Tumor Microenvironment: A Mathematical Model of Glioma Treatment

Abstract

In this paper, we analyze the dynamics of oncolytic virotherapy combined with MEK inhibitors for the treatment of glioma. Although the therapeutic effect of oncolytic viruses (OV) depends on the recruitment of NK cells, these viruses are frequently subject to NK cell clearance, which may reduce the efficacy of oncolytic virotherapy. Furthermore, it is more challenging for OV to enter glioma cells because these cells lack Coxsackievirus and Adenovirus Receptors (CAR). MEK inhibitors, however, are able to compensate for this deficiency in CAR molecules. Herein, we propose and analyze a mathematical model of the dynamics of cancer cells, oncolytic viruses, activated NK cells, and CAR molecules while combining oncolytic virotherapy with MEK inhibition. Our goal is to identify the circumstances in which the treatment may be effective. In this research, we investigated the existence of equilibrium points. The two endemic equilibriums and the virus infection-free equilibrium stability conditions are given. The findings demonstrate that, in a dynamical system, NK cell activation can either establish or destroy equilibrium points and that substantial recruitment of activated NK cells might have detrimental effects on oncolytic virotherapy. However, MEK inhibitors boost OV effectiveness and may prevent NK cell recruitment.