A new dawn for eosinophils in the tumour microenvironment

Abstract

Eosinophils are evolutionarily conserved, pleotropic cells that display key effector functions in allergic diseases, such as asthma. Nonetheless, eosinophils infiltrate multiple tumours and are equipped to regulate tumour progression either directly by interacting with tumour cells or indirectly by shaping the tumour microenvironment (TME). Eosinophils can readily respond to diverse stimuli and are capable of synthesizing and secreting a large range of molecules, including unique granule proteins that can potentially kill tumour cells. Alternatively, they can secrete pro-angiogenic and matrix-remodelling soluble mediators that could promote tumour growth. Herein, we aim to comprehensively outline basic eosinophil biology that is directly related to their activity in the TME. We discuss the mechanisms of eosinophil homing to the TME and examine their diverse pro-tumorigenic and antitumorigenic functions. Finally, we present emerging data regarding eosinophils as predictive biomarkers and effector cells in immunotherapy, especially in response to immune checkpoint blockade therapy, and highlight outstanding questions for future basic and clinical cancer research.

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Fig. 1: Eosinophil maturation and homing into the tumour microenvironment.
Fig. 2: Antitumorigenic activities of eosinophils.
Fig. 3: Pro-tumorigenic activities of eosinophils.
Fig. 4: Eosinophils as biomarkers or therapeutic targets of emerging therapies.

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Acknowledgements

A.M. is supported by the US–Israel Bi-national Science Foundation (grant no. 2011244), the Israel Science Foundation (grant no. 886/15), the Israel Cancer Research Foundation, the Cancer Biology Research Center, Tel Aviv University and the Emerson Collective. This work was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH. A.M. thanks the Munitz laboratory for their excellent input and discussions over the past years.

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S.G, A.D.K. and A.M. researched data for the article, substantially contributed to discussion of content and wrote, reviewed and edited the manuscript before submission. M.I. substantially contributed to discussion of content and to writing the manuscript.

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Correspondence to Ariel Munitz.

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A.M. dedicates this Review to the memory of James J. Lee, who inspired and encouraged his work on defining the role of eosinophils in the tumour microenvironment.

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Nature Reviews Cancer thanks S. Dougan, G. Schiavoni and P. Weller for their contribution to the peer review of this work.

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Glossary

Pathogen-associated molecular patterns

Small molecular motifs derived from microorganisms that can be recognized by specialized pattern recognition receptors.

Extracellular DNA traps

A network of mitochondrial DNA fibres and eosinophil granule proteins, such as major basic protein (MBP) and eosinophil cationic protein (ECP), which facilitate bacterial clearance.

Lipid bodies

(Also known as lipid droplets.) Functionally active organelles that are actively formed within cells from the immune system in response to different inflammatory conditions and are sites for synthesis and storage of inflammatory mediators.

Damage-associated molecular patterns

Host cell-derived biomolecules that can be recognized by pattern recognition receptors to initiate inflammatory responses.

Type 2 T helper (TH2) cell immune responses

TH2 cell responses involve production of cytokines, such as interleukin-4 (IL-4), which stimulate antibody production. TH2 cytokines promote secretory immune responses of mucosal surfaces to extracellular pathogens and allergic reactions.

Absolute eosinophil count

A clinical and pathological measurement that is used to define eosinophil numbers by calculating the percentage of peripheral blood eosinophils multiplied by the total white blood cell count.

Type 2 innate lymphoid cells

Tissue-resident innate immune cells that are derived from a common lymphoid progenitor and are involved in the reaction to parasites and allergic diseases.

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Grisaru-Tal, S., Itan, M., Klion, A.D. et al. A new dawn for eosinophils in the tumour microenvironment. Nat Rev Cancer 20, 594–607 (2020). https://doi.org/10.1038/s41568-020-0283-9

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