Effects Of Macrophages On Tumor Evolution In Microenvironment

The microenvironment mediate many important biological functions in tumor progress.The abundance of tumor-associated macrophages(TAMs)in microenvironment mediate much important biological functions in tumor progress.TAMs present two subtypes:classically activated macrophages(M1)and alternatively activated macrophages(M2).M1 cells facilitate immunological response against tumor.M2 macrophages not only inhibit the function of effector cells to kill tumors but also stimulate tumor angiogenesis,propagation,invasion and metastasis.TAMs have critical effect on tumor and immune interaction.Hence,significant attention has been drawn towards these TAMs.In this paper,the role of the tumor microenvironments during tumorigenesis and the treatment strategies and the interaction between TAMs and tumors are reviewed respectively.On the basis of these studies,we provide theoretical models to investigate the dynamics process and regulatory mechanism between macrophages and tumor immune cells based on the Kuznetsov model.We get main results as follows through theoretical analysis and numerical simulations:We only consider the interactions between M1 macrophages,tumor cells and effect cells in the early stages of tumor progress.By increasing the killing rate of tumor cells by M1 macrophages or increasing the activation rate of effector cells by M1 macrophages or increasing the inflow rate of M1 macrophages,the progression of tumor cells can be inhibited,and even eliminate the tumor cells.Considering the existence of two different subtypes of TAMs and constructing a competition model.The results of interaction dynamics process indicate that M1 macrophages can inhibit the propagation of tumors,and M2 macrophage can promote the development of tumors.The polarization rate of M1 macrophage to M2 macrophage can promote the development of tumor.With the increase of the polarization rate from M1 cells to M2 cells,the system changes from stable state to unstable state,corresponding to tumor from controllable state to uncontrollable state.We construct a simple model by considering the interaction between TAMs and tumors merely.The results show that increasing the activation rate of M2 macrophages by tumor cells and the re-polarisation rate from M2 cells to M1 cells can promote tumor evolution.The dynamics system transitions from a steady state to an unstable state.The above results were corresponding to the immune editing of tumor.We can qualitatively analyze the impact of TAMs on tumor evolution and analyze the stage of tumor and better understand the mechanism of tumor progress.This means that targeting macrophages is a promising cancer immunotherapy strategy.The combination of macrophage targeted therapy with traditional immunotherapy may be a new approach to the treatment of tumors...