Fig. 3: OSDR reconstructs breast cancer fibroblast and macrophage dynamics in agreement with in vitro experiments.
a, Statistical inference using IMC data from 715 human breast cancer biopsies2 captures a wide range of division probabilities based on cell counts in the neighbourhood. Each dot corresponds to a subset of 4,000 cells (859,710 cells in total). b, The breast cancer microenvironment includes interactions between cancer-associated fibroblasts and macrophages. The illustration was created by Nigel Orme. c, The in vitro co-culture experiments of Mayer et al.8 followed fibroblast and macrophage cells in breast cancer conditioned medium (red arrows) or standard medium (grey arrows) to establish a phase portrait with several fixed points (coloured circles).The arrows are changes in cell concentration over 4 days. Panel c was reproduced from ref. 8, Springer Nature Ltd, under a Creative Commons licence CC BY 4.0. d, Ki67 marker in fibroblasts as a function of neighbourhood composition (Methods). Each point corresponds to one fibroblast (69,873 cells), and its position is the composition of the neighbourhood of that cell. The blue line separates inferred regions of rising and falling cell numbers (inferred nullcline). The black contours represent density. e, Same as d but for macrophages (3,761 cells). f, OSDR inferred phase portrait for breast cancer-associated fibroblasts and macrophages. Black, black–white and white circles are stable, semi-stable and unstable fixed points, respectively. g, Phase portraits of fibroblasts and macrophages in an OSDR model that includes tumour cells. The panels show sections of the 3D phase portrait at low (left) or high (right) tumour density (tumour cells fixed at zero or at their mean density of 64 cells per neighbourhood, respectively). Circles are as in g. h, Kaplan–Meier curves for patients whose biopsies indicate hot or cold fibrosis (defined by a macrophage density of more than the halfway point between hot and cold fibrosis fixed points). The hot-fibrosis state is associated with poor prognosis (log-rank test P = 0.0046, n = 607 patients with associated clinical data). The shading indicates 95% confidence intervals based on Greenwood’s exponential formula38.
