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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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.
The authors declare no competing interests.
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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- 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