The re-polarisation of M2 and M1 macrophages and its role on cancer outcomes

The anti-tumour and pro-tumour roles of Th1/Th2 immune cells and M1/M2 macrophages have been documented by numerous experimental studies. However, it is still unknown how these immune cells interact with each other to control tumour dynamics. Here, we use a mathematical model for the interactions between mouse melanoma cells, Th2/Th1 cells and M2/M1 macrophages, to investigate the unknown role of the re-polarisation between M1 and M2 macrophages on tumour growth. The results show that tumour growth is associated with a type-II immune response described by large numbers of Th2 and M2 cells. Moreover, we show that (i) the ratio k of the transition rates k12 (for the re-polarisation M1→M2M1→M2) and k21 (for the re-polarisation M2→M1) is important in reducing tumour population, and (ii) the particular values of these transition rates control the delay in tumour growth and the final tumour size. We also perform a sensitivity analysis to investigate the effect of various model parameters on changes in the tumour cell population, and confirm that the ratio k alone and the ratio of M2 and M1 macrophage populations at earlier times (e.g., day 7) cannot always predict the final tumour size.