AUTHOR=Kareva Irina , Luddy Kimberly A. , O’Farrelly Cliona , Gatenby Robert A. , Brown Joel S. TITLE=Predator-Prey in Tumor-Immune Interactions: A Wrong Model or Just an Incomplete One? JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.668221 DOI=10.3389/fimmu.2021.668221 ISSN=1664-3224 ABSTRACT=

Tumor-immune interactions are often framed as predator-prey. This imperfect analogy describes how immune cells (the predators) hunt and kill immunogenic tumor cells (the prey). It allows for evaluation of tumor cell populations that change over time during immunoediting and it also considers how the immune system changes in response to these alterations. However, two aspects of predator-prey type models are not typically observed in immuno-oncology. The first concerns the conversion of prey killed into predator biomass. In standard predator-prey models, the predator relies on the prey for nutrients, while in the tumor microenvironment the predator and prey compete for resources (e.g. glucose). The second concerns oscillatory dynamics. Standard predator-prey models can show a perpetual cycling in both prey and predator population sizes, while in oncology we see increases in tumor volume and decreases in infiltrating immune cell populations. Here we discuss the applicability of predator-prey models in the context of cancer immunology and evaluate possible causes for discrepancies. Key processes include “safety in numbers”, resource availability, time delays, interference competition, and immunoediting. Finally, we propose a way forward to reconcile differences between model predictions and empirical observations. The immune system is not just predator-prey. Like natural food webs, the immune-tumor community of cell types forms an immune-web of different and identifiable interactions.