Mathematical investigation of the role of re-polarisation of M2 in cancer therapy

Abstract

<p style='text-indent:20px;'>Tumor-associated macrophages are one of the important immune cells in tumor microenvironment and they have both anti-tumor and pro-tumor roles as determined by their phenotypes. Recent experiments have shown that repolarizing pro-tumor M2 into anti-tumor M1 is a feasible antitumor therapy. Here we propose a mathematical model for the tumor-macrophage interactions with M2 re-polarisation delay to investigate the effect of M2 re-polarisation on tumor growth/decay. By using stability and bifurcation theories of DDE, we study the dynamic of this model analytically and numerically and find that the varies of M2 re-polarisation rate and time delay can cause complex dynamical behaviors such as the changes of stabilities of tumor-free, large and small tumor equilibria, the occurrences of saddle-node, Hopf, homoclinic and B-T bifurcation, etc. Moreover, our study reveals that the increase of M2 re-polarisation rate related to immunotherapeutic agent dose can control the tumor to small tumor dormancy and even eliminate the tumor, but this is not always available when immune escape occurs; Pharmacodynamic delay (M2 re-polarisation delay) also affects tumor progression and may cause persistent oscillatory behavior. In addition, the results also indicate the possibility of pseudo-progression in tumor therapy and efficacy of postoperative M2 re-polarisation therapy to prevent tumor recurrence.</p>