Fig. 5: OSDR predicts the collapse of the tumour cell population in responders based on early-treatment biopsies.
a, Longitudinal triple-negative breast cancer dataset by Wang et al.3 includes a total of 141 patients in the chemotherapy arm and 138 patients in the chemotherapy + immunotherapy arm. The illustration was created by Nigel Orme. b, Longitudinal predictions for six cell types. OSDR models were fit separately to early-treatment biopsies from responders (47 and 49 patients in the chemotherapy and chemotherapy + immunotherapy arms, respectively) and non-responders (54 and 57 patients in the chemotherapy and chemotherapy + immunotherapy arms, respectively) in each treatment arm (a total of 140,118 and 157,347 cells in responders and non-responders, respectively, in the chemotherapy arm; 135,559 and 144,261 cells in the chemotherapy + immunotherapy arm, respectively). The tumour cell population collapses in responders (dark grey line) but is stable in non-responders (red line). To isolate the effect of the tumour microenvironment dynamics, as opposed to initial tissue composition, trajectories were computed starting from the composition of all biopsies taken at the beginning of treatment. Plots display the average cell count over all trajectories. The shading denotes 95% confidence intervals of the mean (bootstrap)39. c, Fraction of dividing tumour cells in all neighbourhoods (n = 41,117 and 17,932 cancer cells from non-responders and responders, respectively) and in neighbourhoods with the top 10% of T cells. The error bars display 95% confidence intervals of the mean (bootstrap)39. We compared the fraction of Ki67+ cancer cells in responders versus non-responders using chi-squared tests of independence in all neighbourhoods (left) and in high T cell neighbourhoods (right). Both cases had P < 10−7. d, Zoomed in view of the first 90 days of predicted chemotherapy + immunotherapy treatment response dynamics. The T cell density increases in both responders and non-responders, and the tumour cell population collapses only in responders. The shading denotes 95% confidence intervals of the mean (bootstrap)39.
