Fig. 2.

Schematic of model and approach to parameter estimation and hypothesis testing. a) The four cell types in the model: including melanoma cells, activated CD8⁺ T cells, exhausted CD8⁺ T cells and TAMs. b) Schematic depicting melanoma cells, macrophages, activated CD8⁺ T cells, and exhausted CD8⁺ T cells on the ICS lattice. CD8⁺ T cells and macrophages are free to diffuse around the slide. c) Cell–cell interactions in the model include lysis of melanoma cells by activated CD8⁺ T cells at rate l, exhaustion of activated CD8⁺ T cells by melanoma cells at rate $b_C$ and exhaustion of activated CD8⁺ T cells by TAMs at rate $b_M$. Rates and rules are given in Table S1. Figures (a), (b) and (c) were created with BioRender.com. d) Shows spatial locations of melanoma cells, macrophages, cytotoxic CD8⁺ T cells, and exhausted CD8⁺ T cells from IMC data of human melanoma biopsies taken before ICI treatment and corresponding computationally time-evolved samples after 2 days. Top: IMC slide 06RD corresponding to a responder. Bottom: IMC 19BL corresponding to a nonresponder. Right: Melanoma cell population trajectories in time for 50 samples for each of the 2 slides. The 19BL samples display cancer growth showing nonresponse, and the 06RD samples display cancer regression, which is an example of response.