title: The re-polarisation of M2 and M1 macrophages and its role on cancer outcomes.
abstract: 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→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.
authors.affiliation: Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Lincoln 7476, New Zealand; Division of Mathematics, University of Dundee, Dundee DD1 4HN, United Kingdom; Division of Cancer Research, University of Dundee, Dundee DD1 9SY, United Kingdom. Electronic address: nicoline.vanloenen@lincolnuni.ac.nz.
authors.forename: Nicoline Y
authors.initials: NY
authors.lastname: den Breems
authors.affiliation: Division of Mathematics, University of Dundee, Dundee DD1 4HN, United Kingdom. Electronic address: r.a.eftimie@dundee.ac.uk.
authors.forename: Raluca
authors.initials: R
authors.lastname: Eftimie
mesh_terms: D000465:Algorithms; D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D002452:Cell Count; D045744:Cell Line, Tumor; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000145:classification / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018448:Models, Immunological; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors; D047368:Tumor Burden / Q000276:immunology
keywords: Cancer modelling; M1 and M2 macrophages; MSC: 92C50; Th1 and Th2 immune cells