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Tumour immunotherapy: lessons from predator–prey theory

Abstract

With the burgeoning use of immune-based treatments for cancer, never has there been a greater need to understand the tumour microenvironment within which immune cells function and how it can be perturbed to inhibit tumour growth. Yet, current challenges in identifying optimal combinations of immunotherapies and engineering new cell-based therapies highlight the limitations of conventional paradigms for the study of the tumour microenvironment. Ecology has a rich history of studying predator–prey dynamics to discern factors that drive prey to extinction. Here, we describe the basic tenets of predator–prey theory as applied to ‘predation’ by immune cells and the ‘extinction’ of cancer cells. Our synthesis reveals fundamental mechanisms by which antitumour immunity might fail in sometimes counterintuitive ways and provides a fresh yet evidence-based framework to better understand and therapeutically target the immune–cancer interface.

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Fig. 1: Similarities and differences between the predator–prey and immunity–cancer cycles.
Fig. 2: Functional responses.
Fig. 3: Variation in target cell density suppresses overall immune responses owing to Jensen’s inequality.

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Acknowledgements

Earlier drafts of this work benefited greatly from input and discussion with P. Abrams, J. J. Lum, S. Perlman and A. M. Rodriguez. We apologize to the many authors whose work we were unable to cite owing to space constraints.

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Correspondence to Brad H. Nelson.

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Hamilton, P.T., Anholt, B.R. & Nelson, B.H. Tumour immunotherapy: lessons from predator–prey theory. Nat Rev Immunol 22, 765–775 (2022). https://doi.org/10.1038/s41577-022-00719-y

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