Inferring long-range interactions between immune and tumor cells -- pitfalls and (partial) solutions

Abstract: Upcoming immunotherapies for cancer treatment rely on the ability of the immune system to detect and eliminate tumors in the body. A highly simplified version of this process can be studied in a Petri dish: starting with a random distribution of immune and tumor cells, it can be observed in detail how individual immune cells migrate towards nearby tumor cells, establish contact, and attack. Nevertheless, it remains unclear whether the immune cells find their targets by chance, or if they approach them 'on purpose', using remote sensing mechanisms such as chemotaxis. In this work, we present methods to infer the strength and range of long-range cell-cell interactions from time-lapse recorded cell trajectories, using a maximum likelihood method to fit the model parameters. First, we model the interactions as a distance-dependent 'force' that attracts immune cells towards their nearest tumor cell. While this approach correctly recovers the interaction parameters of simulated cells with constant migration properties, it detects spurious interactions in the case of independent cells that spontaneously change their migration behavior over time. We therefore use an alternative approach that models the interactions by distance-dependent probabilities for positive and negative turning angles of the migrating immune cell. We demonstrate that the latter approach finds the correct interaction parameters even with temporally switching cell migration.