Fig. 5
From: Acidity promotes tumour progression by altering macrophage phenotype in prostate cancer

Acid-responsive macrophages promote tumour growth in silico. a Interaction network for agent-based model illustrating how macrophages and cells interact with, and are affected by, the microenvironment, which is composed of glucose, oxygen, acid, necrotic cells and pro- and anti-inflammatory cytokines. Green lines reflect promotion, while red lines indicate inhibitory interactions. b Output of linear model fitting of Arg1 and Ccl2 expression represented as heatmap. For each phenotypic trait, a linear model allows to predict expression under a variety of conditions. Here, −1 is a tumour-rich inflammatory environment, while 1 is environment with necrosis and anti-inflammatory cytokines. The circles outlined in white are the actual in vitro data. c Snapshots from agent-based model. In the pH window, low pH is dark red, while high pH is yellow. In the cell window, grey pixels are normal cells, white are vessels, and tumour cells are coloured by their phenotype. In the macrophage window, each macrophage is coloured by the mix of CCL2 and ARG1 expressed. Top panel is early in the simulation, bottom panel is when the tumour has taken >90% of the domain and the simulation is stopped. d Simulated survival curves generated after running the simulation under two scenarios, one hundred times each. The “pH Insensitive Macrophage” scenario is where macrophages are not affected by pH, while macrophage behaviour is affected by acid in the “pH Sensitive Macrophage” scenario. Here survival time is the amount of time it took the tumour to take >90% of the domain, given a maximum amount of time of 10 years. Mantel–Haenszel test reveals that these survival curves are significantly different, with p < 0.05