Opposing roles of eosinophils in cancer

  • Sonja C. S. Simon
  • Jochen Utikal
  • Viktor UmanskyEmail author
Focussed Research Review


Eosinophils are a subset of granulocytes mostly known for their ability to combat parasites and induce allergy. Although they were described to be related to cancer more than 100 years ago, their role in tumors is still undefined. Recent observations revealed that they display regulatory functions towards other immune cell subsets in the tumor microenvironment or direct cytotoxic functions against tumor cells, leading to either antitumor or protumor effects. This paradoxical role of eosinophils was suggested to be dependent on the different factors in the TME. In addition, the clinical relevance of these cells has been recently addressed. In most cases, the accumulation of eosinophils both in the tumor tissue, called tumor-associated tissue eosinophilia, and in the peripheral blood were reported to be prognostic markers for a better outcome of cancer patients. In immunotherapy of cancer, particularly in therapy with immune checkpoint inhibitors, eosinophils were even shown to be a potential predictive marker for a beneficial clinical response. A better understanding of their role in cancer progression will help to establish them as prognostic and predictive markers and to design strategies for targeting eosinophils.


Eosinophils Cancer Prognostic marker Immunotherapy PIVAC 17 



Absolute eosinophil count


CC-chemokine ligand


CC-chemokine receptor


Colorectal cancer


C-X-C-chemokine ligand


Damage-associated molecular patterns


Disease-free survival


Dipeptidylpeptidase 4


Eosinophil cationic protein


Eosinophil-derived neurotoxin




High-mobility group box 1 protein


High power fields


Immune checkpoint inhibitor


Major basic protein


Malignant melanoma


Oral squamous cell carcinoma


Pathogen-associated molecular patterns


Progression free survival


Relative eosinophil count


Sialic acid-binding immunoglobulin-like lectin


Tumor-associated tissue eosinophilia


Type 2 Th cells



The authors wish to thank Elisabeth Cordell for editing the manuscript, Xiaoying Hu for designing figure elements, Rebekka Weber and Zeno Riester for helpful advice. The literature search was assisted by Maurizio Grilli from the library for the Medical Faculty of Mannheim, Ruprecht-Karl University of Heidelberg.

Author contributions

SCSS: writing, review and revision of the manuscript, preparation and revision of the figure and table. JU: review and revision of the manuscript. VU: writing, review and revision of the manuscript and revision of the table and figure.


This work was supported by grants from the German Research Council (RTG2099) to J. Utikal and V. Umansky and the Cooperation between German Cancer Research Center (DKFZ) and Ministry of Science, Technology and Space of Israel (MOST) in Cancer Research (CA181 to V. Umansky). This work was kindly backed by the COST Action BM1404 Mye-EUNITER ( COST is supported by the EU Framework Program Horizon 2020.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Vakkila J, Lotze MT (2004) Inflammation and necrosis promote tumour growth. Nat Rev Immunol 4(8):641–648. CrossRefPubMedGoogle Scholar
  2. 2.
    Carretero R, Sektioglu IM, Garbi N, Salgado OC, Beckhove P, Hammerling GJ (2015) Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8(+) T cells. Nat Immunol 16(6):609–609+. CrossRefPubMedGoogle Scholar
  3. 3.
    Lucarini V, Ziccheddu G, Macchia I, La Sorsa V, Peschiaroli F, Buccione C, Sistigu A, Sanchez M, Andreone S, D’Urso MT, Spada M, Macchia D, Afferni C, Mattei F, Schiavoni G (2017) IL-33 restricts tumor growth and inhibits pulmonary metastasis in melanoma-bearing mice through eosinophils. Oncoimmunology. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Legrand F, Driss V, Delbeke M, Loiseau S, Hermann E, Dombrowicz D, Capron M (2010) Human eosinophils exert TNF-alpha and granzyme A-mediated tumoricidal activity toward colon carcinoma cells. J Immunol (Baltim Md 1950) 185(12):7443–7451. CrossRefGoogle Scholar
  5. 5.
    Rosenberg HF, Dyer KD, Foster PS (2013) Eosinophils: changing perspectives in health and disease. Nat Rev Immunol 13(1):9–22. CrossRefPubMedGoogle Scholar
  6. 6.
    Rothenberg ME, Hogan SP (2006) The eosinophil. Annu Rev Immunol 24:147–174. CrossRefGoogle Scholar
  7. 7.
    Weller PF, Spencer LA (2017) Functions of tissue-resident eosinophils. Nat Rev Immunol 17(12):746–760. CrossRefPubMedGoogle Scholar
  8. 8.
    Floyd H, Ni J, Cornish AL, Zeng Z, Liu D, Carter KC, Steel J, Crocker PR (2000) Siglec-8. A novel eosinophil-specific member of the immunoglobulin superfamily. J Biol Chem 275(2):861–866CrossRefGoogle Scholar
  9. 9.
    Dyer KD, Garcia-Crespo KE, Killoran KE, Rosenberg HF (2011) Antigen profiles for the quantitative assessment of eosinophils in mouse tissues by flow cytometry. J Immunol Methods 369(1–2):91–97. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Stevens WW, Kim TS, Pujanauski LM, Hao X, Braciale TJ (2007) Detection and quantitation of eosinophils in the murine respiratory tract by flow cytometry. J Immunol Methods 327(1–2):63–74. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Gleich GJ, Adolphson CR, Leiferman KM (1993) The biology of the eosinophilic leukocyte. Annu Rev Med 44:85–101. CrossRefPubMedGoogle Scholar
  12. 12.
    Upadhyaya B, Yin Y, Hill BJ, Douek DC, Prussin C (2011) Hierarchical IL-5 expression defines a subpopulation of highly differentiated human Th2 cells. J Immunol (Baltim Md 1950) 187(6):3111–3120. CrossRefGoogle Scholar
  13. 13.
    Nussbaum JC, Van Dyken SJ, von Moltke J, Cheng LE, Mohapatra A, Molofsky AB, Thornton EE, Krummel MF, Chawla A, Liang HE, Locksley RM (2013) Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 502(7470):245–248. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Clutterbuck EJ, Hirst EM, Sanderson CJ (1989) Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF. Blood 73(6):1504–1512PubMedGoogle Scholar
  15. 15.
    Farne HA, Wilson A, Powell C, Bax L, Milan SJ (2017) Anti-IL5 therapies for asthma. Cochrane Database Syst Rev 9:CD010834. CrossRefPubMedGoogle Scholar
  16. 16.
    Collins PD, Marleau S, Griffiths-Johnson DA, Jose PJ, Williams TJ (1995) Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med 182(4):1169–1174CrossRefGoogle Scholar
  17. 17.
    Daugherty BL, Siciliano SJ, DeMartino JA, Malkowitz L, Sirotina A, Springer MS (1996) Cloning, expression, and characterization of the human eosinophil eotaxin receptor. J Exp Med 183(5):2349–2354CrossRefGoogle Scholar
  18. 18.
    Kvarnhammar AM, Cardell LO (2012) Pattern-recognition receptors in human eosinophils. Immunology 136(1):11–20. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Dvorak AM, Estrella P, Ishizaka T (1994) Vesicular transport of peroxidase in human eosinophilic myelocytes. Clin Exp Allergy 24(1):10–18CrossRefGoogle Scholar
  20. 20.
    Domachowske JB, Dyer KD, Bonville CA, Rosenberg HF (1998) Recombinant human eosinophil-derived neurotoxin/RNase 2 functions as an effective antiviral agent against respiratory syncytial virus. J Infect Dis 177(6):1458–1464CrossRefGoogle Scholar
  21. 21.
    Lehrer RI, Szklarek D, Barton A, Ganz T, Hamann KJ, Gleich GJ (1989) Antibacterial properties of eosinophil major basic protein and eosinophil cationic protein. J Immunol (Baltim Md 1950) 142(12):4428–4434Google Scholar
  22. 22.
    von Kockritz-Blickwede M, Nizet V (2009) Innate immunity turned inside-out: antimicrobial defense by phagocyte extracellular traps. J Mol Med (Berl) 87(8):775–783. CrossRefGoogle Scholar
  23. 23.
    Yousefi S, Gold JA, Andina N, Lee JJ, Kelly AM, Kozlowski E, Schmid I, Straumann A, Reichenbach J, Gleich GJ, Simon HU (2008) Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat Med 14(9):949–953. CrossRefPubMedGoogle Scholar
  24. 24.
    Jacobsen EA, Ochkur SI, Pero RS, Taranova AG, Protheroe CA, Colbert DC, Lee NA, Lee JJ (2008) Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells. J Exp Med 205(3):699–710. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Chu VT, Frohlich A, Steinhauser G, Scheel T, Roch T, Fillatreau S, Lee JJ, Lohning M, Berek C (2011) Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nat Immunol 12(2):151–159. CrossRefGoogle Scholar
  26. 26.
    Minai-Fleminger Y, Elishmereni M, Vita F, Soranzo MR, Mankuta D, Zabucchi G, Levi-Schaffer F (2010) Ultrastructural evidence for human mast cell-eosinophil interactions in vitro. Cell Tissue Res 341(3):405–415. CrossRefPubMedGoogle Scholar
  27. 27.
    Wen T, Rothenberg ME (2016) The regulatory function of eosinophils. Microbiol Spectr. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Shi HZ, Humbles A, Gerard C, Jin Z, Weller PF (2000) Lymph node trafficking and antigen presentation by endobronchial eosinophils. J Clin Invest 105(7):945–953. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Huang L, Appleton JA (2016) Eosinophils in Helminth Infection: Defenders and Dupes. Trends Parasitol 32(10):798–807. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Linch SN, Kelly AM, Danielson ET, Pero R, Lee JJ, Gold JA (2009) Mouse eosinophils possess potent antibacterial properties in vivo. Infect Immun 77(11):4976–4982. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Phipps S, Lam CE, Mahalingam S, Newhouse M, Ramirez R, Rosenberg HF, Foster PS, Matthaei KI (2007) Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus. Blood 110(5):1578–1586. CrossRefPubMedGoogle Scholar
  32. 32.
    Bedoya VI, Boasso A, Hardy AW, Rybak S, Shearer GM, Rugeles MT (2006) Ribonucleases in HIV type 1 inhibition: effect of recombinant RNases on infection of primary T cells and immune activation-induced RNase gene and protein expression. AIDS Res Hum Retrovir 22(9):897–907. CrossRefPubMedGoogle Scholar
  33. 33.
    Chu VT, Beller A, Rausch S, Strandmark J, Zanker M, Arbach O, Kruglov A, Berek C (2014) Eosinophils promote generation and maintenance of immunoglobulin-A-expressing plasma cells and contribute to gut immune homeostasis. Immunity 40(4):582–593. CrossRefPubMedGoogle Scholar
  34. 34.
    Throsby M, Herbelin A, Pleau JM, Dardenne M (2000) CD11c + eosinophils in the murine thymus: developmental regulation and recruitment upon MHC class I-restricted thymocyte deletion. J Immunol (Baltim Md 1950) 165(4):1965–1975CrossRefGoogle Scholar
  35. 35.
    Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM (2011) Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332(6026):243–247. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Mazzeo C, Canas JA, Zafra MP, Rojas Marco A, Fernandez-Nieto M, Sanz V, Mittelbrunn M, Izquierdo M, Baixaulli F, Sastre J, Del Pozo V (2015) Exosome secretion by eosinophils: a possible role in asthma pathogenesis. J Allergy Clin Immunol 135(6):1603–1613. CrossRefPubMedGoogle Scholar
  37. 37.
    Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O’Byrne PM (2009) Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 360(10):985–993. CrossRefGoogle Scholar
  38. 38.
    Gorriz Gil C, Matallana Royo V, Alvarez Montero O, Rodriguez Valiente A, Fernandez Manzano C, Conde Garcia B, Garcia-Berrocal JR (2018) Eosinophilic esophagitis: an underdiagnosed cause of dysphagia and food impaction to be recognized by otolaryngologists. HNO. CrossRefPubMedGoogle Scholar
  39. 39.
    Gotlib J (2017) World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management. Am J Hematol 92(11):1243–1259. CrossRefPubMedGoogle Scholar
  40. 40.
    Navabi B, Upton JE (2016) Primary immunodeficiencies associated with eosinophilia. Allergy Asthma Clin Immunol 12:27. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Feldbausch F (1900) The occurrence of eosinophilic leukocytes in tumours. Archiv Fur Pathologische Anatomie Physiologie Fur Klinische Medicin 161(1):1–18Google Scholar
  42. 42.
    Huang M, Wang J, Lee P, Sharma S, Mao JT, Meissner H, Uyemura K, Modlin R, Wollman J, Dubinett SM (1995) Human non-small cell lung cancer cells express a type 2 cytokine pattern. Cancer Res 55(17):3847–3853PubMedGoogle Scholar
  43. 43.
    Pandit R, Scholnik A, Wulfekuhler L, Dimitrov N (2007) Non-small-cell lung cancer associated with excessive eosinophilia and secretion of interleukin-5 as a paraneoplastic syndrome. Am J Hematol 82(3):234–237. CrossRefPubMedGoogle Scholar
  44. 44.
    Curran CS, Evans MD, Bertics PJ (2011) 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(3):1254–1263. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Tepper RI, Coffman RL, Leder P (1992) An eosinophil-dependent mechanism for the antitumor effect of interleukin-4. Science 257(5069):548–551CrossRefGoogle Scholar
  46. 46.
    Mattes J, Hulett M, Xie W, Hogan S, Rothenberg ME, Foster P, Parish C (2003) Immunotherapy of cytotoxic T cell-resistant tumors by T helper 2 cells: an eotaxin and STAT6-dependent process. J Exp Med 197(3):387–393CrossRefGoogle Scholar
  47. 47.
    Simson L, Ellyard JI, Dent LA, Matthaei KI, Rothenberg ME, Foster PS, Smyth MJ, Parish CR (2007) Regulation of carcinogenesis by IL-5 and CCL11: A potential role for eosinophils in tumor immune surveillance. J Immunol 178(7):4222–4229. CrossRefPubMedGoogle Scholar
  48. 48.
    Lorena SCM, Oliveira DT, Dorta RG, Landman G, Kowalski LP (2003) Eotaxin expression in oral squamous cell carcinomas with and without tumour associated tissue eosinophilia. Oral Dis 9(6):279–283. CrossRefPubMedGoogle Scholar
  49. 49.
    Hirai H, Fujishita T, Kurimoto K, Miyachi H, Kitano S, Inamoto S, Itatani Y, Saitou M, Maekawa T, Taketo MM (2014) CCR1-mediated accumulation of myeloid cells in the liver microenvironment promoting mouse colon cancer metastasis. Clin Exp Metastasis 31(8):977–989. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Cormier SA, Taranova AG, Bedient C, Nguyen T, Protheroe C, Pero R, Dimina D, Ochkur SI, O’Neill K, Colbert D, Lombari TR, Constant S, McGarry MP, Lee JJ, Lee NA (2006) Pivotal advance: Eosinophil infiltration of solid tumors is an early and persistent inflammatory host response. J Leukoc Biol 79(6):1131–1139. CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Lotfi R, Herzog GI, DeMarco RA, Beer-Stolz D, Lee JJ, Rubartelli A, Schrezenmeier H, Lotze MT (2009) Eosinophils oxidize damage-associated molecular pattern molecules derived from stressed cells. J Immunol (Baltim Md 1950) 183(8):5023–5031. CrossRefGoogle Scholar
  52. 52.
    Kobayashi T, Soma T, Noguchi T, Nakagome K, Nakamoto H, Kita H, Nagata M (2015) ATP drives eosinophil effector responses through P2 purinergic receptors. Allergol Int 64(Suppl):S30–S36. CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    da Silva JM, Queiroz-Junior CM, Batista AC, Rachid MA, Teixeira MM, da Silva TA (2014) Eosinophil depletion protects mice from tongue squamous cell carcinoma induced by 4-nitroquinoline-1-oxide. Histol Histopathol 29(3):387–396. CrossRefGoogle Scholar
  54. 54.
    Wong DTW, Bowen SM, Elovic A, Gallagher GT, Weller PF (1999) Eosinophil ablation and tumor development. Oral Oncol 35(5):496–501. CrossRefPubMedGoogle Scholar
  55. 55.
    O’Flaherty SM, Sutummaporn K, Haggtoft WL, Worrall AP, Rizzo M, Braniste V, Hoglund P, Kadri N, Chambers BJ (2017) TLR-stimulated eosinophils mediate recruitment and activation of NK cells in vivo. Scand J Immunol 85(6):417–424. CrossRefPubMedGoogle Scholar
  56. 56.
    Lotfi R, Lotze MT (2008) Eosinophils induce DC maturation, regulating immunity. J Leukoc Biol 83(3):456–460. CrossRefPubMedGoogle Scholar
  57. 57.
    Xing Y, Tian Y, Kurosawa T, Matsui S, Touma M, Yanai T, Wu Q, Sugimoto K (2016) CCL11-induced eosinophils inhibit the formation of blood vessels and cause tumor necrosis. Genes Cells 21(6):624–638. CrossRefPubMedGoogle Scholar
  58. 58.
    Kubo H, Loegering DA, Adolphson CR, Gleich GJ (1999) Cytotoxic properties of eosinophil granule major basic protein for tumor cells. Int Arch Allergy Immunol 118(2–4):426–428. CrossRefPubMedGoogle Scholar
  59. 59.
    Furbert-Harris PM, Smith MA, Law MP, Currie E, Young JM, Gause DP, Vaughn TR, Harris VL, Oredipe OA (2005) Eosinophil granular protein major basic protein combines with tumor necrosis factor alpha to kill prostate multicellular spheroids in vitro. J Immunother 28(6):619–619. CrossRefGoogle Scholar
  60. 60.
    Costain DJ, Guha AK, Liwski RS, Lee TDG (2001) Murine hypodense eosinophils induce tumour cell apoptosis by a granzyme B-dependent mechanism. Cancer Immunol Immunother 50(6):293–299. CrossRefPubMedGoogle Scholar
  61. 61.
    Caruso RA, Parisi A, Quattrocchi E, Scardigno M, Branca G, Parisi C, Luciano R, Paparo D, Fedele F (2011) Ultrastructural descriptions of heterotypic aggregation between eosinophils and tumor cells in human gastric carcinomas. Ultrastruct Pathol 35(4):145–149. CrossRefPubMedGoogle Scholar
  62. 62.
    Gatault S, Delbeke M, Driss V, Sarazin A, Dendooven A, Kahn JE, Lefevre G, Capron M (2015) 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(5):2483–2492. CrossRefPubMedGoogle Scholar
  63. 63.
    Zaynagetdinov R, Sherrill TP, Gleaves LA, McLoed AG, Saxon JA, Habermann AC, Connelly L, Dulek D, Peebles RS Jr, Fingleton B, Yull FE, Stathopoulos GT, Blackwell TS (2015) Interleukin-5 facilitates lung metastasis by modulating the immune microenvironment. Cancer Res 75(8):1624–1634. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Kratochvill F, Neale G, Haverkamp JM, Van de Velde LA, Smith AM, Kawauchi D, McEvoy J, Roussel MF, Dyer MA, Qualls JE, Murray PJ (2015) TNF counterbalances the emergence of M2 tumor macrophages. Cell Rep 12(11):1902–1914. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB (2002) Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J Exp Med 196(4):459–468CrossRefGoogle Scholar
  66. 66.
    Astigiano S, Morandi B, Costa R, Mastracci L, D’Agostino A, Ratto GB, Melioli G, Frumento G (2005) Eosinophil granulocytes account for indoleamine 2,3-dioxygenase-mediated immune escape in human non-small cell lung cancer. Neoplasia 7(4):390–396. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Puxeddu I, Berkman N, Nissim Ben Efraim AH, Davies DE, Ribatti D, Gleich GJ, Levi-Schaffer F (2009) The role of eosinophil major basic protein in angiogenesis. Allergy 64(3):368–374. CrossRefPubMedGoogle Scholar
  68. 68.
    Varricchi G, Galdiero MR, Loffredo S, Lucarini V, Marone G, Mattei F, Marone G, Schiavoni G (2018) Eosinophils: the unsung heroes in cancer? Oncoimmunology 7(2):e1393134. CrossRefPubMedGoogle Scholar
  69. 69.
    Looi LM (1987) Tumor-associated tissue eosinophilia in nasopharyngeal carcinoma. A pathologic study of 422 primary and 138 metastatic tumors. Cancer 59(3):466–470CrossRefGoogle Scholar
  70. 70.
    Dorta RG, Landman G, Kowalski LP, Lauris JRP, Latorre M, Oliveira DT (2002) Tumour-associated tissue eosinophilia as a prognostic factor in oral squamous cell carcinomas. Histopathology 41(2):152–157. CrossRefPubMedGoogle Scholar
  71. 71.
    Jain D, Tikku G, Bhadana P, Dravid C, Grover RK (2017) The impact of peritumoral retraction clefting & intratumoral eosinophils on overall survival in oral squamous carcinoma patients. Pathol Oncol Res. CrossRefPubMedGoogle Scholar
  72. 72.
    Peurala E, Tuominen M, Loyttyniemi E, Syrjanen S, Rautava J (2018) Eosinophilia is a favorable prognostic marker for oral cavity and lip squamous cell carcinoma. APMIS: acta pathologica, microbiologica, et immunologica Scandinavica 126(3):201–207. CrossRefPubMedGoogle Scholar
  73. 73.
    Oliveira DT, Biassi TP, Faustino SE, Carvalho AL, Landman G, Kowalski LP (2012) Eosinophils may predict occult lymph node metastasis in early oral cancer. Clin Oral Investig 16(6):1523–1528. CrossRefPubMedGoogle Scholar
  74. 74.
    Rakesh N, Devi Y, Majumdar K, Reddy SS, Agarwal K (2015) Tumour associated tissue eosinophilia as a predictor of locoregional recurrence in oral squamous cell carcinoma. J Clin Exp Dent 7(1):e1–e6. CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Alrawi SJ, Tan D, Stoler DL, Dayton M, Anderson GR, Mojica P, Douglas W, Hicks W Jr, Rigual N, Loree T (2005) Tissue eosinophilic infiltration: a useful marker for assessing stromal invasion, survival and locoregional recurrence in head and neck squamous neoplasia. Cancer J 11(3):217–225CrossRefGoogle Scholar
  76. 76.
    Tostes Oliveira D, Tjioe KC, Assao A, Sita Faustino SE, Lopes Carvalho A, Landman G, Kowalski LP (2009) Tissue eosinophilia and its association with tumoral invasion of oral cancer. Int J Surg Pathol 17(3):244–249. CrossRefPubMedGoogle Scholar
  77. 77.
    Moezzi J, Gopalswamy N, Haas RJ, Markert RJ, Suryaprasad S, Bhutani MS (2000) Stromal eosinophilia in colonic epithelial neoplasms. Am J Gastroenterol 95(2):520–523CrossRefGoogle Scholar
  78. 78.
    Kiziltas S, Sezgin Ramadan S, Topuzoglu A, Kullu S (2008) Does the severity of tissue eosinophilia of colonic neoplasms reflect their malignancy potential? Turk J Gastroenterol 19(4):239–244PubMedGoogle Scholar
  79. 79.
    Cho H, Lim SJ, Won KY, Bae GE, Kim GY, Min JW, Noh BJ (2016) Eosinophils in colorectal neoplasms associated with expression of CCL11 and CCL24. J Pathol transl Med 50(1):45–51. CrossRefPubMedGoogle Scholar
  80. 80.
    Prizment AE, Vierkant RA, Smyrk TC, Tillmans LS, Lee JJ, Sriramarao P, Nelson HH, Lynch CF, Thibodeau SN, Church TR, Cerhan JR, Anderson KE, Limburg PJ (2016) Tumor eosinophil infiltration and improved survival of colorectal cancer patients: Iowa Women’s Health Study. Mod Pathol 29(5):516–527. CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Prizment AE, Anderson KE, Visvanathan K, Folsom AR (2011) Inverse association of eosinophil count with colorectal cancer incidence: atherosclerosis risk in communities study. Cancer Epidemiol Biomark Prev 20 (9):1861–1864. CrossRefGoogle Scholar
  82. 82.
    Wei Y, Zhang X, Wang G, Zhou Y, Luo M, Wang S, Hong C (2018) The impacts of pretreatment circulating eosinophils and basophils on prognosis of stage - colorectal cancer. Asia Pacific J Clin Oncol. CrossRefGoogle Scholar
  83. 83.
    Ownby HE, Roi LD, Isenberg RR, Brennan MJ (1983) Peripheral lymphocyte and eosinophil counts as indicators of prognosis in primary breast-cancer. Cancer 52 (1):126–130.;2-y CrossRefPubMedGoogle Scholar
  84. 84.
    Gunduz S, Goksu SS, Arslan D, Tatli AM, Uysal M, Gunduz UR, Sevinc MM, Coskun HS, Bozcuk H, Mutlu H, Savas B (2015) Factors affecting disease-free survival in patients with human epidermal growth factor receptor 2-positive breast cancer who receive adjuvant trastuzumab. Mol Clin Oncol 3(5):1109–1112. CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Xie F, Liu LB, Shang WQ, Chang KK, Meng YH, Mei J, Yu JJ, Li DJ, Li MQ (2015) The infiltration and functional regulation of eosinophils induced by TSLP promote the proliferation of cervical cancer cell. Cancer Lett 364(2):106–117. CrossRefPubMedGoogle Scholar
  86. 86.
    vanDriel WJ, Hogendoorn PCW, Jansen FW, Zwinderman AH, Trimbos JP, Fleuren GJ (1996) Tumor-associated eosinophilic infiltrate of cervical cancer is indicative for ex less effective immune response. Hum Pathol 27(9):904–911. CrossRefGoogle Scholar
  87. 87.
    Bethwaite PB, Holloway LJ, Yeong ML, Thornton A (1993) Effect of tumor-assoicated tissue eosinophilia on survival of women with stage-IB carcinoma of the uterine cervix. J Clin Pathol 46(11):1016–1020. CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Iwasaki K, Torisu M, Fujimura T (1986) Malignant-tumor and eosinophils. 1. Prognostic-significance in gastric-cancer. Cancer 58 (6):1321–1327.;2-o CrossRefPubMedGoogle Scholar
  89. 89.
    Cuschieri A, Talbot I, Weeden S (2002) Influence of pathological tumour variables on long-term survival in resectable gastric cancer. Br J Cancer 86(5):674–679. CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Zhang Y, Ren H, Wang L, Ning Z, Zhuang Y, Gan J, Chen S, Zhou D, Zhu H, Tan D, Zhang H (2014) Clinical impact of tumor-infiltrating inflammatory cells in primary small cell esophageal carcinoma. Int J Mol Sci 15(6):9718–9734. CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Ishibashi S, Ohashi Y, Suzuki T, Miyazaki S, Moriya T, Satomi S, Sasano H (2006) Tumor-associated tissue eosinophilia in human esophageal squamous cell carcinoma. Anticancer Res 26(2B):1419–1424Google Scholar
  92. 92.
    Steel JL, Kim KH, Dew MA, Unruh ML, Antoni MH, Olek MC, Geller DA, Carr BI, Butterfield LH, Gamblin TC (2010) Cancer-related symptom clusters, eosinophils, and survival in hepatobiliary cancer: an exploratory study. J Pain Symptom Manag 39(5):859–871. CrossRefGoogle Scholar
  93. 93.
    Wang HK, Wan FN, Gu WJ, Zhu Y, Dai B, Shi GH, Zhang HL, Ye DW (2016) Eosinophil percentage elevation as a prognostic factor for overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor. Oncotarget 7(42):68943–68953. CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Huland E, Huland H (1992) Tumor-associated eosinophilia in interleukin-2-treated patients: evidence of toxic eosinophil degranulation on bladder cancer cells. J Cancer Res Clin Oncol 118(6):463–467CrossRefGoogle Scholar
  95. 95.
    Sosman JA, Bartemes K, Offord KP, Kita H, Fisher SG, Kefer C, Ellis TA, Fisher RI, Higgins TJ, Gerald GJ (1995) 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(8):805–812PubMedGoogle Scholar
  96. 96.
    Bristol JA, Zhu M, Ji H, Mina M, Xie Y, Clarke L, Forry-Schaudies S, Ennist DL (2003) In vitro and in vivo activities of an oncolytic adenoviral vector designed to express GM-CSF. Mol Ther 7(6):755–764CrossRefGoogle Scholar
  97. 97.
    Weide B, Martens A, Hassel JC, Berking C, Postow MA, Bisschop K, Simeone E, Mangana J, Schilling B, Di Giacomo AM, Brenner N, Kahler K, Heinzerling L, Gutzmer R, Bender A, Gebhardt C, Romano E, Meier F, Martus P, Maio M, Blank C, Schadendorf D, Dummer R, Ascierto PA, Hospers G, Garbe C, Wolchok JD (2016) Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab. Clin Cancer Res 22(22):5487–5496. CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Gebhardt C, Sevko A, Jiang H, Lichtenberger R, Reith M, Tarnanidis K, Holland-Letz T, Umansky L, Beckhove P, Sucker A, Schadendorf D, Utikal J, Umansky V (2015) Myeloid cells and related chronic inflammatory factors as novel predictive markers in melanoma treatment with ipilimumab. Clin Cancer Res 21(24):5453–5459. CrossRefPubMedGoogle Scholar
  99. 99.
    Moreira A, Leisgang W, Schuler G, Heinzerling L (2017) Eosinophilic count as a biomarker for prognosis of melanoma patients and its importance in the response to immunotherapy. Immunotherapy 9(2):115–121. CrossRefPubMedGoogle Scholar
  100. 100.
    Heppt MV, Heinzerling L, Kahler KC, Forschner A, Kirchberger MC, Loquai C, Meissner M, Meier F, Terheyden P, Schell B, Herbst R, Goppner D, Kiecker F, Rafei-Shamsabadi D, Haferkamp S, Huber MA, Utikal J, Ziemer M, Bumeder I, Pfeiffer C, Schad SG, Schmid-Tannwald C, Tietze JK, Eigentler TK, Berking C (2017) Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition. Eur J Cancer (Oxf Engl 1990) 82:56–65. CrossRefGoogle Scholar
  101. 101.
    Tanizaki J, Haratani K, Hayashi H, Chiba Y, Nakamura Y, Yonesaka K, Kudo K, Kaneda H, Hasegawa Y, Tanaka K, Takeda M, Ito A, Nakagawa K (2018) Peripheral blood biomarkers associated with clinical outcome in non-small cell lung cancer patients treated with nivolumab. J Thorac Oncol 13(1):97–105. CrossRefPubMedGoogle Scholar
  102. 102.
    Shelton A, Green RH, Bradding P, Free CM (2010) Peripheral blood eosinophil count correlates with survival in lung cancer. Lung Cancer (Amst Neth) 67:S40–S41. CrossRefGoogle Scholar
  103. 103.
    McNeel DG, Gardner TA, Higano CS, Kantoff PW, Small EJ, Wener MH, Sims RB, DeVries T, Sheikh NA, Dreicer R (2014) 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(10):988–999. CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Legrand F, Klion AD (2015) Biologic therapies targeting eosinophils: current status and future prospects. J Allergy Clin Immunol Pract 3(2):167–174. CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Hollande C, da Silva RB, Bondet V, Llibre A, Duffy D, Mallet V, Pol S, Albert M (2017) DPP4 inhibition reveals interleukin-33-dependent eosinophil-mediated tumor immunity in hepatocellular carcinoma. J Hepatol 66(1):S225–S225. CrossRefGoogle Scholar
  106. 106.
    Liu LY, Bates ME, Jarjour NN, Busse WW, Bertics PJ, Kelly EA (2007) Generation of Th1 and Th2 chemokines by human eosinophils: evidence for a critical role of TNF-alpha. J Immunol (Baltim Md 1950) 179(7):4840–4848CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Skin Cancer Unit, Clinical Cooperation Unit Dermato-OncologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.Department of Dermatology, Venereology and AllergologyUniversity Medical Center Mannheim, Ruprecht-Karl University of HeidelbergMannheimGermany

Personalised recommendations