TY - JOUR
T1 - The re-polarisation of M2 and M1 macrophages and its role on cancer outcomes
AU - den Breems, Nicoline Y.
AU - Eftimie, Raluca
N1 - N.dB. acknowledges support from the BIOMICS project (EU FP7 Grant no. 318202). R.E. acknowledges support from an Engineering and Physical Sciences Research Council (UK) Grant no. EP/K033689/1 and a Northern Research Partnership (Scotland) grant.
PY - 2016/2/7
Y1 - 2016/2/7
N2 - 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.
AB - 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.
KW - Cancer modelling
KW - M1 and M2 macrophages
KW - Th1 and Th2 immune cells
KW - MSC: 92C50
UR - http://www.scopus.com/record/display.uri?eid=2-s2.0-84948428535&origin=resultslist&sort=plf-f&src=s&st1=The+re-polarisation+of+M2+and+M1+macrophages+and+its+role+on+cancer+outcomes&st2=dundee&sid=4445006DF3EE84D2D6063513C421DE6A.53bsOu7mi7A1NSY7fPJf1g%3a1770&sot=b&sdt=b&sl=292&s=TITLE-ABS-KEY%28The+re-polarisation+of+M2+and+M1+macrophages+and+its+role+on+cancer+outcomes%29+AND+SUBJAREA%28MULT+OR+AGRI+OR+BIOC+OR+IMMU+OR+NEUR+OR+PHAR+OR+MULT+OR+MEDI+OR+NURS+OR+VETE+OR+DENT+OR+HEAL+OR+MULT+OR+ARTS+OR+BUSI+OR+DECI+OR+ECON+OR+PSYC+OR+SOCI%29+AND+PUBYEAR+%3E+2013+AND+PUBYEAR+%3C+2017&relpos=0&citeCnt=1&searchTerm=
U2 - 10.1016/j.jtbi.2015.10.034
DO - 10.1016/j.jtbi.2015.10.034
M3 - Article
C2 - 26551154
SN - 0022-5193
VL - 390
SP - 23
EP - 39
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
ER -