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A new dawn for eosinophils in the tumour microenvironment

Nature Reviews Cancer volume 20, pages 594–607 (2020)Cite this article

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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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References

  1. Reinbach, G. Ueber das Verhalten der Leukocyten bei malignen Tumoren. Arch. f. Klin. Chir 46, 486–562 (1983).

    Google Scholar 

  2. Lee, J. J., Jacobsen, E. A., McGarry, M. P., Schleimer, R. P. & Lee, N. A. Eosinophils in health and disease: the LIAR hypothesis. Clin. Exp. Allergy 40, 563–575 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Rosenberg, H. F., Dyer, K. D. & Foster, P. S. Eosinophils: changing perspectives in health and disease. Nat. Rev. Immunol. 13, 9–22 (2013).

    CAS  PubMed  Google Scholar 

  4. Rothenberg, M. E. & Hogan, S. P. The eosinophil. Annu. Rev. Immunol. 24, 147–174 (2006).

    CAS  PubMed  Google Scholar 

  5. Andersen, C. L. et al. Association of the blood eosinophil count with hematological malignancies and mortality. Am. J. Hematol. 90, 225–229 (2015).

    CAS  PubMed  Google Scholar 

  6. Fulkerson, P. C. Transcription factors in eosinophil development and as therapeutic targets. Front. Med. 4, 115 (2017).

    Google Scholar 

  7. Sanderson, C. J. Interleukin-5, eosinophils, and disease. Blood 79, 3101–3109 (1992).

    CAS  PubMed  Google Scholar 

  8. Collins, P. D., Marleau, S., Griffiths Johnson, D. A., Jose, P. J. & Williams, T. J. Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J. Exp. Med. 182, 1169–1174 (1995).

    CAS  PubMed  Google Scholar 

  9. Rothenberg, M. E. et al. IL-5-dependent conversion of normodense human eosinophils to the hypodense phenotype uses 3T3 fibroblasts for enhanced viability, accelerated hypodensity, and sustained antibody-dependent cytotoxicity. J. Immunol. 143, 2311–2316 (1989).

    CAS  PubMed  Google Scholar 

  10. Weller, P. F. & Spencer, L. A. Functions of tissue-resident eosinophils. Nat. Rev. Immunol. 17, 746–760 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Lee, J. J. et al. Human versus mouse eosinophils: “that which we call an eosinophil, by any other name would stain as red”. J. Allergy Clin. Immunol. 130, 572–584 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Lewis, D. M., Lewis, J. C., Loegering, D. A. & Gleich, G. J. Localization of the guinea pig eosinophil major basic protein to the core of the granule. J. Cell Biol. 77, 702–713 (1978).

    CAS  PubMed  Google Scholar 

  13. Egesten, A., Alumets, J., von Mecklenburg, C., Palmegren, M. & Olsson, I. Localization of eosinophil cationic protein, major basic protein, and eosinophil peroxidase in human eosinophils by immunoelectron microscopic technique. J. Histochem. Cytochem. 34, 1399–1403 (1986).

    CAS  PubMed  Google Scholar 

  14. Spencer, L. A. et al. Human eosinophils constitutively express multiple Th1, Th2, and immunoregulatory cytokines that are secreted rapidly and differentially. J. Leukoc. Biol. 85, 117–123 (2009).

    CAS  PubMed  Google Scholar 

  15. Ayars, G. H., Altman, L. C., Gleich, G. J., Loegering, D. A. & Baker, C. B. Eosinophil- and eosinophil granule-mediated pneumocyte injury. J. Allergy Clin. Immunol. 76, 595–604 (1985).

    CAS  PubMed  Google Scholar 

  16. Hamann, K. J. et al. In vitro killing of microfilariae of Brugia pahangi and Brugia malayi by eosinophil granule proteins. J. Immunol. 144, 3166–3173 (1990).

    CAS  PubMed  Google Scholar 

  17. Hisamatsu, K. et al. Cytotoxicity of human eosinophil granule major basic protein to human nasal sinus mucosa in vitro. J. Allergy Clin. Immunol. 86, 52–63 (1990).

    CAS  PubMed  Google Scholar 

  18. Kubo, H., Loegering, D. A., Adolphson, C. R. & Gleich, G. J. Cytotoxic properties of eosinophil granule major basic protein for tumor cells. Int. Arch. Allergy Immunol. 118, 426–428 (1999).

    CAS  PubMed  Google Scholar 

  19. Arlandson, M. et al. Eosinophil peroxidase oxidation of thiocyanate. Characterization of major reaction products and a potential sulfhydryl-targeted cytotoxicity system. J. Biol. Chem. 276, 215–224 (2001).

    CAS  PubMed  Google Scholar 

  20. MacPherson, J. C. et al. Eosinophils are a major source of nitric oxide-derived oxidants in severe asthma: characterization of pathways available to eosinophils for generating reactive nitrogen species. J. Immunol. 166, 5763–5772 (2001).

    CAS  PubMed  Google Scholar 

  21. Rosenberg, H. F. RNase a ribonucleases and host defense: an evolving story. J. Leukoc. Biol. 83, 1079–1087 (2008).

    CAS  PubMed  Google Scholar 

  22. Ueki, S. et al. Eosinophil extracellular DNA trap cell death mediates lytic release of free secretion-competent eosinophil granules in humans. Blood 121, 2074–2083 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Melo, R. C. & Weller, P. F. Unraveling the complexity of lipid body organelles in human eosinophils. J. Leukoc. Biol. 96, 703–712 (2014).

    PubMed  PubMed Central  Google Scholar 

  24. Patel, V. P. et al. Molecular and functional characterization of two novel human C-C chemokines as inhibitors of two distinct classes of myeloid progenitors. J. Exp. Med. 185, 1163–1172 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Forssmann, U. et al. Eotaxin-2, a novel CC chemokine that is selective for the chemokine receptor CCR3, and acts like eotaxin on human eosinophil and basophil leukocytes. J. Exp. Med. 185, 2171–2176 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Shinkai, A. et al. A novel human CC chemokine, eotaxin-3, which is expressed in IL-4-stimulated vascular endothelial cells, exhibits potent activity toward eosinophils. J. Immunol. 163, 1602–1610 (1999).

    CAS  PubMed  Google Scholar 

  27. Zimmermann, N., Hershey, G. K., Foster, P. S. & Rothenberg, M. E. Chemokines in asthma: cooperative interaction between chemokines and IL-13. J. Allergy Clin. Immunol. 111, 227–242; quiz 243 (2003).

    CAS  PubMed  Google Scholar 

  28. Combadiere, C., Ahuja, S. K. & Murphy, P. M. Cloning and functional expression of a human eosinophil CC chemokine receptor. J. Biol. Chem. 270, 16491–16494 (1995).

    CAS  PubMed  Google Scholar 

  29. Ponath, P. D. et al. Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J. Exp. Med. 183, 2437–2448 (1996).

    CAS  PubMed  Google Scholar 

  30. Daugherty, B. L. et al. Cloning, expression, and characterization of the human eosinophil eotaxin receptor. J. Exp. Med. 183, 2349–2354 (1996).

    CAS  PubMed  Google Scholar 

  31. Bertrand, C. P. & Ponath, P. D. CCR3 blockade as a new therapy for asthma. Expert. Opin. Investig. Drugs 9, 43–52 (2000).

    CAS  PubMed  Google Scholar 

  32. Yang, M. et al. Eotaxin-2 and IL-5 cooperate in the lung to regulate IL-13 production and airway eosinophilia and hyperreactivity. J. Allergy Clin. Immunol. 112, 935–943 (2003).

    CAS  PubMed  Google Scholar 

  33. Pope, S. M. et al. IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism. J. Allergy Clin. Immunol. 108, 594–601 (2001).

    CAS  PubMed  Google Scholar 

  34. Ellyard, J. I. et al. Eotaxin selectively binds heparin. An interaction that protects eotaxin from proteolysis and potentiates chemotactic activity in vivo. J. Biol. Chem. 282, 15238–15247 (2007).

    CAS  PubMed  Google Scholar 

  35. Simson, L. et al. Regulation of carcinogenesis by IL-5 and CCL11: a potential role for eosinophils in tumor immune surveillance. J. Immunol. 178, 4222–4229 (2007).

    CAS  PubMed  Google Scholar 

  36. Hung, K. et al. The central role of CD4+ T cells in the antitumor immune response. J. Exp. Med. 188, 2357–2368 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Zaynagetdinov, R. et al. Interleukin-5 facilitates lung metastasis by modulating the immune microenvironment. Cancer Res. 75, 1624–1634 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Ikutani, M. et al. Identification of innate IL-5-producing cells and their role in lung eosinophil regulation and antitumor immunity. J. Immunol. 188, 703–713 (2012).

    CAS  PubMed  Google Scholar 

  39. Cho, H. et al. Eosinophils in colorectal neoplasms associated with expression of CCL11 and CCL24. J. Pathol. Transl. Med. 50, 45–51 (2016).

    PubMed  Google Scholar 

  40. Teruya-Feldstein, J. et al. Differential chemokine expression in tissues involved by Hodgkin’s disease: direct correlation of eotaxin expression and tissue eosinophilia. Blood 93, 2463–2470 (1999).

    CAS  PubMed  Google Scholar 

  41. Lorena, S. C., Oliveira, D. T., Dorta, R. G., Landman, G. & Kowalski, L. P. Eotaxin expression in oral squamous cell carcinomas with and without tumour associated tissue eosinophilia. Oral. Dis. 9, 279–283 (2003).

    CAS  PubMed  Google Scholar 

  42. Reichman, H. et al. Activated eosinophils exert antitumorigenic activities in colorectal cancer. Cancer Immunol. Res. 7, 388–400 (2019). This study is the first to subject intratumoural eosinophils to bulk RNA sequencing, which revealed a potent IFNγ-associated signature for eosinophils that likely mediates their antitumorigenic activities in CRC.

    CAS  PubMed  Google Scholar 

  43. Cheadle, E. J. et al. Eotaxin-2 and colorectal cancer: a potential target for immune therapy. Clin. Cancer Res. 13, 5719–5728 (2007).

    CAS  PubMed  Google Scholar 

  44. Jundt, F. et al. Hodgkin/Reed–Sternberg cells induce fibroblasts to secrete eotaxin, a potent chemoattractant for T cells and eosinophils. Blood 94, 2065–2071 (1999).

    CAS  PubMed  Google Scholar 

  45. Lotfi, R., Lee, J. J. & Lotze, M. T. Eosinophilic granulocytes and damage-associated molecular pattern molecules (DAMPs): role in the inflammatory response within tumors. J. Immunother. 30, 16–28 (2007).

    CAS  PubMed  Google Scholar 

  46. Shik, D., Moshkovits, I., Karo-Atar, D., Reichman, H. & Munitz, A. Interleukin-33 requires CMRF35-like molecule-1 expression for induction of myeloid cell activation. Allergy 69, 719–729 (2014).

    CAS  PubMed  Google Scholar 

  47. Dyer, K. D. & Rosenberg, H. F. Physiologic concentrations of HMGB1 have no impact on cytokine-mediated eosinophil survival or chemotaxis in response to eotaxin-2 (CCL24). PLoS One 10, e0118887 (2015).

    PubMed  PubMed Central  Google Scholar 

  48. Lin, F., Xue, D., Xie, T. & Pan, Z. HMGB1 promotes cellular chemokine synthesis and potentiates mesenchymal stromal cell migration via Rap1 activation. Mol. Med. Rep. 14, 1283–1289 (2016).

    CAS  PubMed  Google Scholar 

  49. Liew, F. Y., Girard, J. P. & Turnquist, H. R. Interleukin-33 in health and disease. Nat. Rev. Immunol. 16, 676–689 (2016).

    CAS  PubMed  Google Scholar 

  50. Liew, F. Y., Pitman, N. I. & McInnes, I. B. Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat. Rev. Immunol. 10, 103–110 (2010).

    CAS  PubMed  Google Scholar 

  51. Pecaric-Petkovic, T., Didichenko, S. A., Kaempfer, S., Spiegl, N. & Dahinden, C. A. Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33. Blood 113, 1526–1534 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Curran, C. S. & Bertics, P. J. Human eosinophils express RAGE, produce RAGE ligands, exhibit PKC-δ phosphorylation and enhanced viability in response to the RAGE ligand, S100B. Int. Immunol. 23, 713–728 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Chu, V. T. et al. Eosinophils promote generation and maintenance of immunoglobulin-A-expressing plasma cells and contribute to gut immune homeostasis. Immunity 40, 582–593 (2014).

    CAS  PubMed  Google Scholar 

  54. Cormier, S. A. et al. Pivotal advance: eosinophil infiltration of solid tumors is an early and persistent inflammatory host response. J. Leukoc. Biol. 79, 1131–1139 (2006).

    CAS  PubMed  Google Scholar 

  55. Lee, J. J. & Lee, N. A. Eosinophil degranulation: an evolutionary vestige or a universally destructive effector function? Clin. Exp. Allergy 35, 986–994 (2005).

    CAS  PubMed  Google Scholar 

  56. Dennis, K. L. et al. Adenomatous polyps are driven by microbe-instigated focal inflammation and are controlled by IL-10-producing T cells. Cancer Res. 73, 5905–5913 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Svensson, L. & Wenneras, C. Human eosinophils selectively recognize and become activated by bacteria belonging to different taxonomic groups. Microbes Infect. 7, 720–728 (2005).

    CAS  PubMed  Google Scholar 

  58. Bruijnzeel, P. L. et al. Eosinophil migration in atopic dermatitis. I: increased migratory responses to N-formyl-methionyl-leucyl-phenylalanine, neutrophil-activating factor, platelet-activating factor, and platelet factor 4. J. Invest. Dermatol. 100, 137–142 (1993).

    CAS  PubMed  Google Scholar 

  59. Svensson, L. et al. House dust mite allergen activates human eosinophils via formyl peptide receptor and formyl peptide receptor-like 1. Eur. J. Immunol. 37, 1966–1977 (2007).

    CAS  PubMed  Google Scholar 

  60. da Silva, J. M. et al. Relevance of CCL3/CCR5 axis in oral carcinogenesis. Oncotarget 8, 51024–51036 (2017).

    PubMed  PubMed Central  Google Scholar 

  61. Hirai, H. et al. CCR1-mediated accumulation of myeloid cells in the liver microenvironment promoting mouse colon cancer metastasis. Clin. Exp. Metastasis 31, 977–989 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Gatault, S., Legrand, F., Delbeke, M., Loiseau, S. & Capron, M. Involvement of eosinophils in the anti-tumor response. Cancer Immunol. Immunother. 61, 1527–1534 (2012).

    PubMed  Google Scholar 

  63. Davis, B. P. & Rothenberg, M. E. Eosinophils and cancer. Cancer Immunol. Res. 2, 1–8 (2014).

    CAS  PubMed  Google Scholar 

  64. Qian, B. Z. & Pollard, J. W. Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39–51 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Biswas, S. K. & Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 11, 889–896 (2010).

    CAS  PubMed  Google Scholar 

  66. Fridlender, Z. G. et al. Polarization of tumor-associated neutrophil phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell 16, 183–194 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Mesnil, C. et al. Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J. Clin. Invest. 126, 3279–3295 (2016). This study reveals two distinct eosinophil populations displaying opposing activities in the lungs of allergen-challenged mice.

    PubMed  PubMed Central  Google Scholar 

  68. Furbert-Harris, P. M. et al. Activated eosinophils upregulate the metastasis suppressor molecule E-cadherin on prostate tumor cells. Cell Mol. Biol. 49, 1009–1016 (2003).

    CAS  PubMed  Google Scholar 

  69. Munitz, A. et al. 2B4 (CD244) is expressed and functional on human eosinophils. J. Immunol. 174, 110–118 (2005).

    CAS  PubMed  Google Scholar 

  70. Kataoka, S., Konishi, Y., Nishio, Y., Fujikawa-Adachi, K. & Tominaga, A. Antitumor activity of eosinophils activated by IL-5 and eotaxin against hepatocellular carcinoma. DNA Cell Biol. 23, 549–560 (2004).

    CAS  PubMed  Google Scholar 

  71. Lucarini, V. et al. IL-33 restricts tumor growth and inhibits pulmonary metastasis in melanoma-bearing mice through eosinophils. Oncoimmunology 6, e1317420 (2017).

    PubMed  PubMed Central  Google Scholar 

  72. Gatault, S. et al. IL-18 is involved in eosinophil-mediated tumoricidal activity against a colon carcinoma cell line by upregulating LFA-1 and ICAM-1. J. Immunol. 195, 2483–2492 (2015).

    CAS  PubMed  Google Scholar 

  73. Legrand, F. et al. Human eosinophils exert TNF-α and granzyme A-mediated tumoricidal activity toward colon carcinoma cells. J. Immunol. 185, 7443–7451 (2010).

    CAS  PubMed  Google Scholar 

  74. Andreone, S. et al. IL-33 promotes CD11b/CD18-mediated adhesion of eosinophils to cancer cells and synapse-polarized degranulation leading to tumor cell killing. Cancers 11, 1664 (2019).

    CAS  PubMed Central  Google Scholar 

  75. Taylor, R., Lee, T. D. & Hoskin, D. W. Adhesion of tumoricidal eosinophils to MCA-38 colon adenocarcinoma cells involves protein tyrosine kinase activation and is diminished by elevated cyclic AMP in the effector cell. Int. J. Oncol. 13, 1305–1311 (1998).

    CAS  PubMed  Google Scholar 

  76. Graziano, R. F., Looney, R. J., Shen, L. & Fanger, M. W. FcγR-mediated killing by eosinophils. J. Immunol. 142, 230–235 (1989).

    CAS  PubMed  Google Scholar 

  77. Furbert-Harris, P. M. et al. Activated eosinophils infiltrate MCF-7 breast multicellular tumor spheroids. Anticancer Res. 23, 71–78 (2003).

    PubMed  Google Scholar 

  78. Mattes, J. et al. Immunotherapy of cytotoxic T cell-resistant tumors by T helper 2 cells: an eotaxin and STAT6-dependent process. J. Exp. Med. 197, 387–393 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Xing, Y. et al. CCL11-induced eosinophils inhibit the formation of blood vessels and cause tumor necrosis. Genes Cell 21, 624–638 (2016).

    CAS  Google Scholar 

  80. Yaffe, L. J. & Finkelman, F. D. Induction of a B-lymphocyte receptor for a T cell-replacing factor by the crosslinking of surface IgD. Proc. Natl Acad. Sci. USA 80, 293–297 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Carretero, R. et al. Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8+ T cells. Nat. Immunol. 16, 609–617 (2015). This elegant study shows that eosinophils shape the TME by regulating the vasculature, and further demonstrates that IFNγ-activated and TNF-activated eosinophils promote tumour rejection by enhancing CD8+ T cell recruitment and skewing macrophage polarization.

    CAS  PubMed  Google Scholar 

  82. Xie, F. et al. The infiltration and functional regulation of eosinophils induced by TSLP promote the proliferation of cervical cancer cell. Cancer Lett. 364, 106–117 (2015).

    CAS  PubMed  Google Scholar 

  83. Zhang, B. et al. TSLP promotes angiogenesis of human umbilical vein endothelial cells by strengthening the crosstalk between cervical cancer cells and eosinophils. Oncol. Lett. 14, 7483–7488 (2017).

    PubMed  PubMed Central  Google Scholar 

  84. Stathopoulos, G. T. et al. Host-derived interleukin-5 promotes adenocarcinoma-induced malignant pleural effusion. Am. J. Respir. Crit. Care Med. 182, 1273–1281 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Eiro, N. et al. Relationship between the inflammatory molecular profile of breast carcinomas and distant metastasis development. PLoS One 7, e49047 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Martinelli-Klay, C. P., Mendis, B. R. & Lombardi, T. Eosinophils and oral squamous cell carcinoma: a short review. J. Oncol. 2009, 310132 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Wong, D. T., Bowen, S. M., Elovic, A., Gallagher, G. T. & Weller, P. F. Eosinophil ablation and tumor development. Oral. Oncol. 35, 496–501 (1999).

    CAS  PubMed  Google Scholar 

  88. Puxeddu, I. et al. Human peripheral blood eosinophils induce angiogenesis. Int. J. Biochem. Cell Biol. 37, 628–636 (2005).

    CAS  PubMed  Google Scholar 

  89. Panagopoulos, V. et al. Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment. Int. J. Oncol. 50, 1191–1200 (2017).

    CAS  PubMed  Google Scholar 

  90. Walsh, M. T., Connell, K., Sheahan, A. M., Gleich, G. J. & Costello, R. W. Eosinophil peroxidase signals via epidermal growth factor-2 to induce cell proliferation. Am. J. Respir. Cell Mol. Biol. 45, 946–952 (2011).

    CAS  PubMed  Google Scholar 

  91. Hennigan, K. et al. Eosinophil peroxidase activates cells by HER2 receptor engagement and β1-integrin clustering with downstream MAPK cell signaling. Clin. Immunol. 171, 1–11 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Curran, C. S., Evans, M. D. & Bertics, P. J. GM-CSF production by glioblastoma cells has a functional role in eosinophil survival, activation, and growth factor production for enhanced tumor cell proliferation. J. Immunol. 187, 1254–1263 (2011).

    CAS  PubMed  Google Scholar 

  93. Yasukawa, A. et al. Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells. PLoS One 8, e64281 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Kratochvill, F. et al. TNF counterbalances the emergence of M2 tumor macrophages. Cell Rep. 12, 1902–1914 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Odemuyiwa, S. O. et al. Cutting edge: human eosinophils regulate T cell subset selection through indoleamine 2,3-dioxygenase. J. Immunol. 173, 5909–5913 (2004).

    CAS  PubMed  Google Scholar 

  96. Astigiano, S. et al. Eosinophil granulocytes account for indoleamine 2,3-dioxygenase-mediated immune escape in human non-small cell lung cancer. Neoplasia 7, 390–396 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Simon, H. U. et al. Interleukin-2 primes eosinophil degranulation in hypereosinophilia and Wells’ syndrome. Eur. J. Immunol. 33, 834–839 (2003).

    CAS  PubMed  Google Scholar 

  98. Sosman, J. A. et al. Evidence for eosinophil activation in cancer patients receiving recombinant interleukin-4: effects of interleukin-4 alone and following interleukin-2 administration. Clin. Cancer Res. 1, 805–812 (1995).

    CAS  PubMed  Google Scholar 

  99. Ellem, K. A. et al. A case report: immune responses and clinical course of the first human use of granulocyte/macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy. Cancer Immunol. Immunother. 44, 10–20 (1997).

    CAS  PubMed  Google Scholar 

  100. Gebhardt, C. et al. Myeloid cells and related chronic inflammatory factors as novel predictive markers in melanoma treatment with ipilimumab. Clin. Cancer Res. 21, 5453–5459 (2015).

    CAS  PubMed  Google Scholar 

  101. Webster, R. M. The immune checkpoint inhibitors: where are we now? Nat. Rev. Drug. Discov. 13, 883–884 (2014).

    CAS  PubMed  Google Scholar 

  102. Pardoll, D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12, 252–264 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Martens, A. et al. Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab. Clin. Cancer Res. 22, 2908–2918 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Lang, B. M. et al. Long-term survival with modern therapeutic agents against metastatic melanoma — vemurafenib and ipilimumab in a daily life setting. Med. Oncol. 35, 24 (2018).

    CAS  PubMed  Google Scholar 

  105. Moreira, A., Leisgang, W., Schuler, G. & Heinzerling, L. Eosinophilic count as a biomarker for prognosis of melanoma patients and its importance in the response to immunotherapy. Immunotherapy 9, 115–121 (2017).

    CAS  PubMed  Google Scholar 

  106. Hude, I. et al. Leucocyte and eosinophil counts predict progression-free survival in relapsed or refractory classical Hodgkin lymphoma patients treated with PD1 inhibition. Br. J. Haematol. 181, 837–840 (2018).

    PubMed  Google Scholar 

  107. Weide, B. et al. Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab. Clin. Cancer Res. 22, 5487–5496 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Rafei-Shamsabadi, D., Lehr, S., von Bubnoff, D. & Meiss, F. Successful combination therapy of systemic checkpoint inhibitors and intralesional interleukin-2 in patients with metastatic melanoma with primary therapeutic resistance to checkpoint inhibitors alone. Cancer Immunol. Immunother. 68, 1417–1428 (2019).

    CAS  PubMed  Google Scholar 

  109. Alenmyr, L. et al. Blockade of CTLA-4 promotes airway inflammation in naive mice exposed to aerosolized allergen but fails to prevent inhalation tolerance. Scand. J. Immunol. 62, 437–444 (2005).

    CAS  PubMed  Google Scholar 

  110. Zheng, X. et al. CTLA4 blockade promotes vessel normalization in breast tumors via the accumulation of eosinophils. Int. J. Cancer 146, 1730–1740 (2020). This study provides the first mechanistic evidence that eosinophils are important effector cells in the antitumour response that is elicited by blockade of CTLA4.

    CAS  PubMed  Google Scholar 

  111. House, I. G. et al. Macrophage-derived CXCL9 and CXCL10 are required for antitumor immune responses following immune checkpoint blockade. Clin. Cancer. Res. 26, 487–504 (2019).

    PubMed  Google Scholar 

  112. Wolf, M. T. et al. A biologic scaffold-associated type 2 immune microenvironment inhibits tumor formation and synergizes with checkpoint immunotherapy. Sci. Transl. Med. 11, eaat7973 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Spolski, R., Li, P. & Leonard, W. J. Biology and regulation of IL-2: from molecular mechanisms to human therapy. Nat. Rev. Immunol. 18, 648–659 (2018).

    CAS  PubMed  Google Scholar 

  114. Rosenberg, S. A. IL-2: the first effective immunotherapy for human cancer. J. Immunol. 192, 5451–5458 (2014).

    CAS  PubMed  Google Scholar 

  115. Van Gool, F. et al. Interleukin-5-producing group 2 innate lymphoid cells control eosinophilia induced by interleukin-2 therapy. Blood 124, 3572–3576 (2014).

    PubMed  PubMed Central  Google Scholar 

  116. Huland, E. & Huland, H. Tumor-associated eosinophilia in interleukin-2-treated patients: evidence of toxic eosinophil degranulation on bladder cancer cells. J. Cancer Res. Clin. Oncol. 118, 463–467 (1992).

    CAS  PubMed  Google Scholar 

  117. Abdel-Wahab, Z. et al. Transduction of human melanoma cells with interleukin-2 gene reduces tumorigenicity and enhances host antitumor immunity: a nude mouse model. Cell Immunol. 159, 26–39 (1994).

    CAS  PubMed  Google Scholar 

  118. Rivoltini, L. et al. In vitro anti-tumor activity of eosinophils from cancer patients treated with subcutaneous administration of interleukin 2. Role of interleukin 5. Int. J. Cancer 54, 8–15 (1993).

    CAS  PubMed  Google Scholar 

  119. Vlad, A. M. et al. A phase II trial of intraperitoneal interleukin-2 in patients with platinum-resistant or platinum-refractory ovarian cancer. Cancer Immunol. Immunother. 59, 293–301 (2010).

    CAS  PubMed  Google Scholar 

  120. Ruffell, B., DeNardo, D. G., Affara, N. I. & Coussens, L. M. Lymphocytes in cancer development: polarization towards pro-tumor immunity. Cytokine Growth Factor Rev. 21, 3–10 (2010).

    CAS  PubMed  Google Scholar 

  121. Reichman, H., Karo-Atar, D. & Munitz, A. Emerging roles for eosinophils in the tumor microenvironment. Trends Cancer 2, 664–675 (2016).

    PubMed  Google Scholar 

  122. Widmer, M. B., Acres, R. B., Sassenfeld, H. M. & Grabstein, K. H. Regulation of cytolytic cell populations from human peripheral blood by B cell stimulatory factor 1 (interleukin 4). J. Exp. Med. 166, 1447–1455 (1987).

    CAS  PubMed  Google Scholar 

  123. Rothenberg, M. E., Luster, A. D. & Leder, P. Murine eotaxin: an eosinophil chemoattractant inducible in endothelial cells and in interleukin 4-induced tumor suppression. Proc. Natl Acad. Sci. USA 92, 8960–8964 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Tepper, R. I., Pattengale, P. K. & Leder, P. Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell 57, 503–512 (1989).

    CAS  PubMed  Google Scholar 

  125. Khazaie, K. et al. Persistence of dormant tumor cells in the bone marrow of tumor cell-vaccinated mice correlates with long-term immunological protection. Proc. Natl Acad. Sci. USA 91, 7430–7434 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Tepper, R. I., Coffman, R. L. & Leder, P. An eosinophil-dependent mechanism for the antitumor effect of interleukin-4. Science 257, 548–551 (1992). This study demonstrates that constitutive expression of IL-4 in athymic nude mice elicits a tumour-associated eosinophil infiltrate associated with decreased tumour growth, stimulating further investigations into the role of eosinophils in cancer.

    CAS  PubMed  Google Scholar 

  127. Saleh, M. The role of tumour-derived mIL-4 on rat C6 glioma regression. Int. J. Oncol. 10, 1223–1227 (1997).

    CAS  PubMed  Google Scholar 

  128. Addison, C., Gauldie, J., Muller, W. & Graham, F. An adenoviral vector expressing interleukin-4 modulates tumorigenicity and induces regression in a murine breast-cancer model. Int. J. Oncol. 7, 1253–1260 (1995).

    CAS  PubMed  Google Scholar 

  129. Gao, K. et al. Transgenic expression of IL-33 activates CD8+ T cells and NK cells and inhibits tumor growth and metastasis in mice. Cancer Lett. 335, 463–471 (2013).

    CAS  PubMed  Google Scholar 

  130. Perales-Puchalt, A. et al. IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment. Oncoimmunology 8, e1515058 (2019).

    PubMed  Google Scholar 

  131. Hollande, C. et al. Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth. Nat. Immunol. 20, 257–264 (2019).

    CAS  PubMed  Google Scholar 

  132. Lu, B., Yang, M. & Wang, Q. Interleukin-33 in tumorigenesis, tumor immune evasion, and cancer immunotherapy. J. Mol. Med. 94, 535–543 (2016).

    CAS  PubMed  Google Scholar 

  133. Dougan, M., Dranoff, G. & Dougan, S. K. GM-CSF, IL-3, and IL-5 family of cytokines: regulators of inflammation. Immunity 50, 796–811 (2019).

    CAS  PubMed  Google Scholar 

  134. Hoeller, C., Michielin, O., Ascierto, P. A., Szabo, Z. & Blank, C. U. Systematic review of the use of granulocyte–macrophage colony-stimulating factor in patients with advanced melanoma. Cancer Immunol. Immunother. 65, 1015–1034 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Dranoff, G. et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte–macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc. Natl Acad. Sci. USA 90, 3539–3543 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. McNeel, D. G. et al. A transient increase in eosinophils is associated with prolonged survival in men with metastatic castration-resistant prostate cancer who receive sipuleucel-T. Cancer Immunol. Res. 2, 988–999 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Correale, P. et al. Second-line treatment of non small cell lung cancer by biweekly gemcitabine and docetaxel ± granulocyte–macrophage colony stimulating factor and low dose aldesleukine. Cancer Biol. Ther. 8, 497–502 (2009).

    CAS  PubMed  Google Scholar 

  138. Yang, D. et al. Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2–MyD88 signal pathway in dendritic cells and enhances Th2 immune responses. J. Exp. Med. 205, 79–90 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Klion, A. D., Ackerman, S. J. & Bochner, B. S. Contributions of eosinophils to human health and disease. Annu. Rev. Pathol. 15, 179–209 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Kuang, F. L. et al. Long-term clinical outcomes of high-dose mepolizumab treatment for hypereosinophilic syndrome. J. Allergy Clin. Immunol. Pract. 6, 1518–1527.e5 (2018).

    PubMed  PubMed Central  Google Scholar 

  141. Murphy, K. et al. Long-term safety and efficacy of reslizumab in patients with eosinophilic asthma. J. Allergy Clin. Immunol. Pract. 5, 1572–1581.e3 (2017).

    PubMed  Google Scholar 

  142. Andersen, C. L. et al. Eosinophilia in routine blood samples as a biomarker for solid tumor development — a study based on the Copenhagen Primary Care Differential Count (CopDiff) database. Acta Oncol. 53, 1245–1250 (2014).

    PubMed  Google Scholar 

  143. Popov, H., Donev, I. S. & Ghenev, P. Quantitative analysis of tumor-associated tissue eosinophilia in recurring bladder cancer. Cureus 10, e3279 (2018).

    PubMed  PubMed Central  Google Scholar 

  144. Lowe, D., Fletcher, C. D. & Gower, R. L. Tumour-associated eosinophilia in the bladder. J. Clin. Pathol. 37, 500–502 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Onesti, C. E. et al. Predictive and prognostic role of peripheral blood eosinophil count in triple-negative and hormone receptor-negative/HER2-positive breast cancer patients undergoing neoadjuvant treatment. Oncotarget 9, 33719–33733 (2018).

    PubMed  PubMed Central  Google Scholar 

  146. Ownby, H. E., Roi, L. D., Isenberg, R. R. & Brennan, M. J. Peripheral lymphocyte and eosinophil counts as indicators of prognosis in primary breast cancer. Cancer 52, 126–130 (1983).

    CAS  PubMed  Google Scholar 

  147. Spiegel, G. W., Ashraf, M. & Brooks, J. J. Eosinophils as a marker for invasion in cervical squamous neoplastic lesions. Int. J. Gynecol. Pathol. 21, 117–124 (2002).

    PubMed  Google Scholar 

  148. van Driel, W. J. et al. Tumor-associated eosinophilic infiltrate of cervical cancer is indicative for a less effective immune response. Hum. Pathol. 27, 904–911 (1996).

    PubMed  Google Scholar 

  149. Prizment, A. E. et al. Tumor eosinophil infiltration and improved survival of colorectal cancer patients: Iowa Women’s Health Study. Mod. Pathol. 29, 516–527 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Fernandez-Acenero, M. J., Galindo-Gallego, M., Sanz, J. & Aljama, A. Prognostic influence of tumor-associated eosinophilic infiltrate in colorectal carcinoma. Cancer 88, 1544–1548 (2000).

    CAS  PubMed  Google Scholar 

  151. Pretlow, T. P. et al. Eosinophil infiltration of human colonic carcinomas as a prognostic indicator. Cancer Res. 43, 2997–3000 (1983).

    CAS  PubMed  Google Scholar 

  152. Ishibashi, S. et al. Tumor-associated tissue eosinophilia in human esophageal squamous cell carcinoma. Anticancer. Res. 26, 1419–1424 (2006).

    PubMed  Google Scholar 

  153. Zhang, Y. et al. Clinical impact of tumor-infiltrating inflammatory cells in primary small cell esophageal carcinoma. Int. J. Mol. Sci. 15, 9718–9734 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Songun, I. et al. Expression of oncoproteins and the amount of eosinophilic and lymphocytic infiltrates can be used as prognostic factors in gastric cancer. Dutch Gastric Cancer Group (DGCG). Br. J. Cancer 74, 1783–1788 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Iwasaki, K., Torisu, M. & Fujimura, T. Malignant tumor and eosinophils. I. Prognostic significance in gastric cancer. Cancer 58, 1321–1327 (1986).

    CAS  PubMed  Google Scholar 

  156. von Wasielewski, R. et al. Tissue eosinophilia correlates strongly with poor prognosis in nodular sclerosing Hodgkin’s disease, allowing for known prognostic factors. Blood 95, 1207–1213 (2000).

    Google Scholar 

  157. Enblad, G., Sundstrom, C. & Glimelius, B. Infiltration of eosinophils in Hodgkin’s disease involved lymph nodes predicts prognosis. Hematol. Oncol. 11, 187–193 (1993).

    CAS  PubMed  Google Scholar 

  158. Said, M. et al. Tissue eosinophilia: a morphologic marker for assessing stromal invasion in laryngeal squamous neoplasms. BMC Clin. Pathol. 5, 1 (2005).

    PubMed  PubMed Central  Google Scholar 

  159. Thompson, A. C., Bradley, P. J. & Griffin, N. R. Tumor-associated tissue eosinophilia and long-term prognosis for carcinoma of the larynx. Am. J. Surg. 168, 469–471 (1994).

    CAS  PubMed  Google Scholar 

  160. Dorta, R. G. et al. Tumour-associated tissue eosinophilia as a prognostic factor in oral squamous cell carcinomas. Histopathology 41, 152–157 (2002).

    CAS  PubMed  Google Scholar 

  161. Jain, M. et al. Assessment of tissue eosinophilia as a prognosticator in oral epithelial dysplasia and oral squamous cell carcinoma—an image analysis study. Pathol. Res. Int. 2014, 507512 (2014).

    Google Scholar 

  162. Rakesh, N., Devi, Y., Majumdar, K., Reddy, S. S. & Agarwal, K. Tumour associated tissue eosinophilia as a predictor of locoregional recurrence in oral squamous cell carcinoma. J. Clin. Exp. Dent. 7, e1–e6 (2015).

    PubMed  PubMed Central  Google Scholar 

  163. Bishara, S. et al. Pre-treatment white blood cell subtypes as prognostic indicators in ovarian cancer. Eur. J. Obstet. Gynecol. Reprod. Biol. 138, 71–75 (2008).

    CAS  PubMed  Google Scholar 

  164. Steel, J. L. et al. Cancer-related symptom clusters, eosinophils, and survival in hepatobiliary cancer: an exploratory study. J. Pain Symptom Manage. 39, 859–871 (2010).

    PubMed  PubMed Central  Google Scholar 

  165. Shinke, G. et al. The postoperative peak number of leukocytes after hepatectomy is a significant prognostic factor for cholangiocarcinoma. Mol. Clin. Oncol. 10, 531–540 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Meyerholz, D. K., Griffin, M. A., Castilow, E. M. & Varga, S. M. Comparison of histochemical methods for murine eosinophil detection in an RSV vaccine-enhanced inflammation model. Toxicol. Pathol. 37, 249–255 (2009).

    PubMed  PubMed Central  Google Scholar 

  167. Yamaguchi, Y. et al. Models of lineage switching in hematopoietic development: a new myeloid-committed eosinophil cell line (YJ) demonstrates trilineage potential. Leukemia 12, 1430–1439 (1998).

    CAS  PubMed  Google Scholar 

  168. Macias, M. P. et al. Identification of a new murine eosinophil major basic protein (mMBP) gene: cloning and characterization of mMBP-2. J. Leukoc. Biol. 67, 567–576 (2000).

    CAS  PubMed  Google Scholar 

  169. Willetts, L. et al. Immunodetection of occult eosinophils in lung tissue biopsies may help predict survival in acute lung injury. Respir. Res. 12, 116 (2011).

    PubMed  PubMed Central  Google Scholar 

  170. Erjefalt, J. S. et al. Degranulation patterns of eosinophil granulocytes as determinants of eosinophil driven disease. Thorax 56, 341–344 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Doyle, A. D. et al. Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils. J. Leukoc. Biol. 94, 17–24 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Grace, J. O. et al. Reuse of public, genome-wide, murine eosinophil expression data for hypotheses development. J. Leukoc. Biol. 104, 185–193 (2018).

    CAS  PubMed  Google Scholar 

  173. Zhu, F., Liu, P., Li, J. & Zhang, Y. Eotaxin-1 promotes prostate cancer cell invasion via activation of the CCR3–ERK pathway and upregulation of MMP-3 expression. Oncol. Rep. 31, 2049–2054 (2014).

    CAS  PubMed  Google Scholar 

  174. Levina, V. et al. Role of eotaxin-1 signaling in ovarian cancer. Clin. Cancer Res. 15, 2647–2656 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Hitoshi, Y. et al. Distribution of IL-5 receptor-positive B cells. Expression of IL-5 receptor on Ly-1(CD5)+ B cells. J. Immunol. 144, 4218–4225 (1990).

    CAS  PubMed  Google Scholar 

  176. Varricchi, G. et al. Eosinophils: the unsung heroes in cancer? Oncoimmunology 7, e1393134 (2018).

    PubMed  Google Scholar 

  177. Chen, B., Khodadoust, M. S., Liu, C. L., Newman, A. M. & Alizadeh, A. A. Profiling tumor infiltrating immune cells with CIBERSORT. Methods Mol. Biol. 1711, 243–259 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

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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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Authors and Affiliations

  1. Department of Clinical Microbiology and Immunology, Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel

    Sharon Grisaru-Tal, Michal Itan & Ariel Munitz

  2. Human Eosinophil Section, Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Amy D. Klion

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  1. Sharon Grisaru-Tal
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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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Dedication

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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