Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Coincident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intratumoral innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the crosstalk between allergic response and cancer is paving the way for new avenues of treatment.

Center Pigmod Institute of Animal Physiology and Genetics Academy of Sciences of Czech Republic Libechov Czech Republic

CIBER Epidemiología y Salud Pública Madrid Spain

Department of Biomedical Sciences Nazarbayev University School of Medicine Astana Kazakhstan

Department of Microbiology Immunology and Molecular Genetics David Geffen School of Medicine at UCLA Los Angeles CA USA

Division of Asthma Allergy and Lung Biology Medical Research Council and Asthma UK Centre in Allergic Mechanisms in Asthma King's College London London UK

Division of Cancer Studies Faculty of Life Sciences and Medicine King's College London Guy's Hospital London UK

Division of Gastroenterology Hepatology and Nutrition Research Department of Medicine Research Children's University Hospital Boston Boston MA USA

Division of Genetics and Molecular Medicine Faculty of Life Sciences and Medicine St John's Institute of Dermatology King's College London London UK

Division of Pharmacology Faculty of Science Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands

Division of Rheumatology Immunology and Allergy Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA

Division of Surgical Oncology Department of Surgery David Geffen School of Medicine at UCLA Los Angeles CA USA

Immunological Engineering Department of Engineering Aarhus University Aarhus Denmark

INSERM CHU Lille European Genomic Institute of Diabetes Institut Pasteur de Lille U1011 récepteurs nucléaires maladies cardiovasculaires et diabète Université de Lille Lille France

Institute of Pathophysiology and Allergy Research Center of Pathophysiology Infectiology and Immunology Medical University Vienna Vienna Austria

IRCCS San Raffaele Scientific Institute Milan Italy

ISGlobal Centre for Research in Environmental Epidemiology Barcelona Spain

Jonsson Comprehensive Cancer Center University of California Los Angeles CA USA

LIRIC Unité Mixte de Recherche 995 INSERM Université de Lille 2 CHRU de Lille Lille France

McLaughlin Centre for Population Health Risk Assessment University of Ottawa Ottawa ON Canada

NIHR Biomedical Research Centre at Guy's and St Thomas' Hospitals and King's College London King's College London Guy's Hospital London UK

Pharmacology and Experimental Therapeutics Unit Faculty of Medicine School of Pharmacy The Institute for Drug Research The Hebrew University of Jerusalem Jerusalem Israel

Randall Division of Cell and Molecular Biophysics King's College London London UK

Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

The Interuniversity Messerli Research Institute University of Veterinary Medicine Vienna Medical University of Vienna Vienna Austria

Universitat Pompeu Fabra Barcelona Spain

Zobrazit více v PubMed

Jensen‐Jarolim E, Achatz G, Turner MC, Karagiannis S, Legrand F, Capron M et al. AllergoOncology: the role of IgE‐mediated allergy in cancer. Allergy 2008;63:1255–1266. PubMed PMC

Penichet ML, Jensen‐Jarolim E, editors. Cancer and IgE: introducing the concept of AllergoOncology. New York, NY: Springer; 2010.

Jensen‐Jarolim E, Pawelec G. The nascent field of AllergoOncology. Cancer Immunol Immunother 2012;61:1355–1357. PubMed PMC

Turner MC. Epidemiology: allergy history, IgE, and cancer. Cancer Immunol Immunother 2012;61:1493–1510. PubMed PMC

Van Hemelrijck M, Garmo H, Binda E, Hayday A, Karagiannis SN, Hammar N et al. Immunoglobulin E and cancer: a meta‐analysis and a large Swedish cohort study. Cancer Causes Control 2010;21:1657–1667. PubMed

Jacobs EJ, Gapstur SM, Newton CC, Turner MC, Campbell PT. Hay Fever and asthma as markers of atopic immune response and risk of colorectal cancer in three large cohort studies. Cancer Epidemiol Biomarkers Prev 2013;22:661–669. PubMed

Linabery AM, Prizment AE, Anderson KE, Cerhan JR, Poynter JN, Ross JA. Allergic diseases and risk of hematopoietic malignancies in a cohort of postmenopausal women: a report from the Iowa Women's Health Study. Cancer Epidemiol Biomarkers Prev 2014;23:1903–1912. PubMed PMC

Platz EA, Drake CG, Wilson KM, Sutcliffe S, Kenfield SA, Mucci LA et al. Asthma and risk of lethal prostate cancer in the Health Professionals Follow‐Up Study. Int J Cancer 2015;137:949–958. PubMed PMC

Cahoon EK, Inskip PD, Gridley G, Brenner AV. Immune‐related conditions and subsequent risk of brain cancer in a cohort of 4.5 million male US veterans. Br J Cancer 2014;110:1825–1833. PubMed PMC

Schwartzbaum J, Ding B, Johannesen TB, Osnes LT, Karavodin L, Ahlbom A et al. Association between prediagnostic IgE levels and risk of glioma. J Natl Cancer Inst 2012;104:1251–1259. PubMed PMC

Schlehofer B, Siegmund B, Linseisen J, Schuz J, Rohrmann S, Becker S et al. Primary brain tumours and specific serum immunoglobulin E: a case‐control study nested in the European Prospective Investigation into Cancer and Nutrition cohort. Allergy 2011;66:1434–1441. PubMed

Wulaningsih W, Holmberg L, Garmo H, Karagiannis S, Ahlstedt S, Malmstrom H et al. Investigating the association between allergen‐specific immunoglobulin E, cancer risk and survival. OncoImmunology 2016;5:e1154250. PubMed PMC

Nieters A, Luczynska A, Becker S, Becker N, Vermeulen R, Overvad K et al. Prediagnostic immunoglobulin E levels and risk of chronic lymphocytic leukemia, other lymphomas and multiple myeloma‐results of the European Prospective Investigation into Cancer and Nutrition. Carcinogenesis 2014;35:2716–2722. PubMed PMC

Olson SH, Hsu M, Wiemels JL, Bracci PM, Zhou M, Patoka J et al. Serum immunoglobulin e and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 2014;23:1414–1420. PubMed PMC

Skaaby T, Nystrup Husemoen LL, Roswall N, Thuesen BH, Linneberg A. Atopy and development of cancer: a population‐based prospective study. J Allergy Clin Immunol Pract 2014;2:779–785. PubMed

Prizment AE, Anderson KE, Visvanathan K, Folsom AR. Inverse association of eosinophil count with colorectal cancer incidence: atherosclerosis risk in communities study. Cancer Epidemiol Biomarkers Prev 2011;20:1861–1864. PubMed PMC

Purdue MP, Lan Q, Kemp TJ, Hildesheim A, Weinstein SJ, Hofmann JN et al. Elevated serum sCD23 and sCD30 up to two decades prior to diagnosis associated with increased risk of non‐Hodgkin lymphoma. Leukemia 2015;29:1429–1431. PubMed PMC

Backes DM, Siddiq A, Cox DG, Calboli FC, Gaziano JM, Ma J et al. Single‐nucleotide polymorphisms of allergy‐related genes and risk of adult glioma. J Neurooncol 2013;113:229–238. PubMed PMC

Josephs DH, Spicer JF, Corrigan CJ, Gould HJ, Karagiannis SN. Epidemiological associations of allergy, IgE and cancer. Clin Exp Allergy 2013;43:1110–1123. PubMed

Karagiannis P, Gilbert AE, Josephs DH, Ali N, Dodev T, Saul L et al. IgG4 subclass antibodies impair antitumor immunity in melanoma. J Clin Invest 2013;123:1457–1474. PubMed PMC

Groot Kormelink T, Powe DG, Kuijpers SA, Abudukelimu A, Fens MH, Pieters EH et al. Immunoglobulin free light chains are biomarkers of poor prognosis in basal‐like breast cancer and are potential targets in tumor‐associated inflammation. Oncotarget 2014;5:3159–3167. PubMed PMC

Andreu P, Johansson M, Affara NI, Pucci F, Tan T, Junankar S et al. FcRgamma activation regulates inflammation‐associated squamous carcinogenesis. Cancer Cell 2010;17:121–134. PubMed PMC

Zennaro D, Capalbo C, Scala E, Liso M, Spillner E, Braren I et al. IgE, IgG4 and IgG response to tissue‐specific and environmental antigens in patients affected by cancer. European Academy of Allergy and Clinical Immunology (EAACI), Istanbul, Turkey, 2011: Abstract 209.

Bluth MH. IgE and chemotherapy. Cancer Immunol Immunother 2012;61:1585–1590. PubMed PMC

Fu SL, Pierre J, Smith‐Norowitz TA, Hagler M, Bowne W, Pincus MR et al. Immunoglobulin E antibodies from pancreatic cancer patients mediate antibody‐dependent cell‐mediated cytotoxicity against pancreatic cancer cells. Clin Exp Immunol 2008;153:401–409. PubMed PMC

Matta GM, Battaglio S, Dibello C, Napoli P, Baldi C, Ciccone G et al. Polyclonal immunoglobulin E levels are correlated with hemoglobin values and overall survival in patients with multiple myeloma. Clin Cancer Res 2007;13:5348–5354. PubMed

Mechtcheriakova D, Svoboda M, Meshcheryakova A, Jensen‐Jarolim E. Activation‐induced cytidine deaminase (AID) linking immunity, chronic inflammation, and cancer. Cancer Immunol Immunother 2012;61:1591–1598. PubMed PMC

Gould HJ, Takhar P, Harries HE, Durham SR, Corrigan CJ. Germinal‐centre reactions in allergic inflammation. Trends Immunol 2006;27:446–452. PubMed

Strid J, Sobolev O, Zafirova B, Polic B, Hayday A. The intraepithelial T cell response to NKG2D‐ligands links lymphoid stress surveillance to atopy. Science 2011;334:1293–1297. PubMed PMC

Finkin S, Yuan D, Stein I, Taniguchi K, Weber A, Unger K et al. Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat Immunol 2015;16:1235–1244. PubMed PMC

Meshcheryakova A, Tamandl D, Bajna E, Stift J, Mittlboeck M, Svoboda M et al. B cells and ectopic follicular structures: novel players in anti‐tumor programming with prognostic power for patients with metastatic colorectal cancer. PLoS One 2014;9:e99008. PubMed PMC

Alphonse MP, Saffar AS, Shan L, HayGlass KT, Simons FE, Gounni AS. Regulation of the high affinity IgE receptor (Fc epsilonRI) in human neutrophils: role of seasonal allergen exposure and Th‐2 cytokines. PLoS One 2008;3:e1921. PubMed PMC

Dehlink E, Baker AH, Yen E, Nurko S, Fiebiger E. Relationships between levels of serum IgE, cell‐bound IgE, and IgE‐receptors on peripheral blood cells in a pediatric population. PLoS One 2010;5:e12204. PubMed PMC

Nakajima K, Kho DH, Yanagawa T, Harazono Y, Hogan V, Chen W et al. Galectin‐3 cleavage alters bone remodeling: different outcomes in breast and prostate cancer skeletal metastasis. Cancer Res 2016;76:1391–1402. PubMed PMC

Tadokoro T, Morishita A, Fujihara S, Iwama H, Niki T, Fujita K et al. Galectin‐9: an anticancer molecule for gallbladder carcinoma. Int J Oncol 2016;48:1165–1174. PubMed

Takano J, Morishita A, Fujihara S, Iwama H, Kokado F, Fujikawa K et al. Galectin‐9 suppresses the proliferation of gastric cancer cells in vitro. Oncol Rep 2016;35:851–860. PubMed

Untersmayr E, Bises G, Starkl P, Bevins CL, Scheiner O, Boltz‐Nitulescu G et al. The high affinity IgE receptor Fc epsilonRI is expressed by human intestinal epithelial cells. PLoS One 2010;5:e9023. PubMed PMC

Dehlink E, Platzer B, Baker AH, Larosa J, Pardo M, Dwyer P et al. A soluble form of the high affinity IgE receptor, Fc‐epsilon‐RI, circulates in human serum. PLoS One 2011;6:e19098. PubMed PMC

Nakajima K, Kho DH, Yanagawa T, Zimel M, Heath E, Hogan V et al. Galectin‐3 in bone tumor microenvironment: a beacon for individual skeletal metastasis management. Cancer Metastasis Rev 2016;35:333–346. PubMed PMC

Marichal T, Tsai M, Galli SJ. Mast cells: potential positive and negative roles in tumor biology. Cancer Immunol Res 2013;1:269–279. PubMed

Maciel TT, Moura IC, Hermine O. The role of mast cells in cancers. F1000Prime Rep 2015;7:09. PubMed PMC

Dalton DK, Noelle RJ. The roles of mast cells in anticancer immunity. Cancer Immunol Immunother 2012;61:1511–1520. PubMed PMC

Khazaie K, Blatner NR, Khan MW, Gounari F, Gounaris E, Dennis K et al. The significant role of mast cells in cancer. Cancer Metastasis Rev 2011;30:45–60. PubMed

Stoyanov E, Uddin M, Mankuta D, Dubinett SM, Levi‐Schaffer F. Mast cells and histamine enhance the proliferation of non‐small cell lung cancer cells. Lung Cancer 2012;75:38–44. PubMed

Rajput AB, Turbin DA, Cheang MC, Voduc DK, Leung S, Gelmon KA et al. Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases. Breast Cancer Res Treat 2008;107:249–257. PubMed PMC

Johansson A, Rudolfsson S, Hammarsten P, Halin S, Pietras K, Jones J et al. Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy. Am J Pathol 2010;177:1031–1041. PubMed PMC

Yang Z, Zhang B, Li D, Lv M, Huang C, Shen GX et al. Mast cells mobilize myeloid‐derived suppressor cells and Treg cells in tumor microenvironment via IL‐17 pathway in murine hepatocarcinoma model. PLoS One 2010;5:e8922. PubMed PMC

Huang B, Lei Z, Zhang GM, Li D, Song C, Li B et al. SCF‐mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment. Blood 2008;112:1269–1279. PubMed PMC

Pittoni P, Tripodo C, Piconese S, Mauri G, Parenza M, Rigoni A et al. Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers. Cancer Res 2011;71:5987–5997. PubMed

Wei JJ, Song CW, Sun LC, Yuan Y, Li D, Yan B et al. SCF and TLR4 ligand cooperate to augment the tumor‐promoting potential of mast cells. Cancer Immunol Immunother 2012;61:303–312. PubMed PMC

Strouch MJ, Cheon EC, Salabat MR, Krantz SB, Gounaris E, Melstrom LG et al. Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clin Cancer Res 2010;16:2257–2265. PubMed PMC

Liu X, Jin H, Zhang G, Lin X, Chen C, Sun J et al. Intratumor IL‐17‐positive mast cells are the major source of the IL‐17 that is predictive of survival in gastric cancer patients. PLoS One 2014;9:e106834. PubMed PMC

de Vries VC, Wasiuk A, Bennett KA, Benson MJ, Elgueta R, Waldschmidt TJ et al. Mast cell degranulation breaks peripheral tolerance. Am J Transplant 2009;9:2270–2280. PubMed PMC

Teo PZ, Utz PJ, Mollick JA. Using the allergic immune system to target cancer: activity of IgE antibodies specific for human CD20 and MUC1. Cancer Immunol Immunother 2012;61:2295–2309. PubMed PMC

Gatault S, Legrand F, Delbeke M, Loiseau S, Capron M. Involvement of eosinophils in the anti‐tumor response. Cancer Immunol Immunother 2012;61:1527–1534. PubMed PMC

Gatault S, Delbeke M, Driss V, Sarazin A, Dendooven A, Kahn JE 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 2015;195:2483–2492. PubMed

Legrand F, Driss V, Delbeke M, Loiseau S, Hermann E, Dombrowicz D et al. Human eosinophils exert TNF‐alpha and granzyme A‐mediated tumoricidal activity toward colon carcinoma cells. J Immunol 2010;185:7443–7451. PubMed

Legrand F, Driss V, Woerly G, Loiseau S, Hermann E, Fournie JJ et al. A functional gammadeltaTCR/CD3 complex distinct from gammadeltaT cells is expressed by human eosinophils. PLoS One 2009;4:e5926. PubMed PMC

Karagiannis SN, Bracher MG, Hunt J, McCloskey N, Beavil RL, Beavil AJ et al. IgE‐antibody‐dependent immunotherapy of solid tumors: cytotoxic and phagocytic mechanisms of eradication of ovarian cancer cells. J Immunol 2007;179:2832–2843. PubMed

Erreni M, Mantovani A, Allavena P. Tumor‐associated macrophages (TAM) and inflammation in colorectal cancer. Cancer Microenviron 2011;4:141–154. PubMed PMC

Beyer M, Mallmann MR, Xue J, Staratschek‐Jox A, Vorholt D, Krebs W et al. High‐resolution transcriptome of human macrophages. PLoS One 2012;7:e45466. PubMed PMC

Roszer T. Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm 2015;2015:816460. PubMed PMC

Van Overmeire E, Laoui D, Keirsse J, Van Ginderachter JA, Sarukhan A. Mechanisms driving macrophage diversity and specialization in distinct tumor microenvironments and parallelisms with other tissues. Front Immunol 2014;5:127. PubMed PMC

Mills CD, Lenz LL, Harris RA. A breakthrough: macrophage‐directed cancer immunotherapy. Cancer Res 2016;76:513–516. PubMed PMC

Ellyard JI, Quah BJ, Simson L, Parish CR. Alternatively activated macrophage possess antitumor cytotoxicity that is induced by IL‐4 and mediated by arginase‐1. J Immunother 2010;33:443–452. PubMed

De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell 2013;23:277–286. PubMed

Miyatani K, Saito H, Murakami Y, Watanabe J, Kuroda H, Matsunaga T et al. A high number of IgG4‐positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis. Virchows Arch 2016;468:549–557. PubMed

Platzer B, Dehlink E, Turley SJ, Fiebiger E. How to connect an IgE‐driven response with CTL activity? Cancer Immunol Immunother 2012;61:1521–1525. PubMed PMC

Platzer B, Elpek KG, Cremasco V, Baker K, Stout MM, Schultz C et al. IgE/FcepsilonRI‐mediated antigen cross‐presentation by dendritic cells enhances anti‐tumor immune responses. Cell Rep 2015;pii:S2211‐1247(15)00143‐6. PubMed PMC

Platzer B, Stout M, Fiebiger E. Functions of dendritic‐cell‐bound IgE in allergy. Mol Immunol 2015;68:116–119. PubMed PMC

Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat Rev Immunol 2006;6:836–848. PubMed

Aspord C, Pedroza‐Gonzalez A, Gallegos M, Tindle S, Burton EC, Su D et al. Breast cancer instructs dendritic cells to prime interleukin 13‐secreting CD4 + T cells that facilitate tumor development. J Exp Med 2007;204:1037–1047. PubMed PMC

Ubukata H, Motohashi G, Tabuchi T, Nagata H, Konishi S, Tabuchi T. Evaluations of interferon‐gamma/interleukin‐4 ratio and neutrophil/lymphocyte ratio as prognostic indicators in gastric cancer patients. J Surg Oncol 2010;102:742–747. PubMed

De Monte L, Reni M, Tassi E, Clavenna D, Papa I, Recalde H et al. Intratumor T helper type 2 cell infiltrate correlates with cancer‐associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J Exp Med 2011;208:469–478. PubMed PMC

Fujisawa T, Joshi B, Nakajima A, Puri RK. A novel role of interleukin‐13 receptor alpha2 in pancreatic cancer invasion and metastasis. Cancer Res 2009;69:8678–8685. PubMed

Francipane MG, Alea MP, Lombardo Y, Todaro M, Medema JP, Stassi G. Crucial role of interleukin‐4 in the survival of colon cancer stem cells. Cancer Res 2008;68:4022–4025. PubMed

Suzuki A, Leland P, Joshi BH, Puri RK. Targeting of IL‐4 and IL‐13 receptors for cancer therapy. Cytokine 2015;75:79–88. PubMed

Schreck S, Friebel D, Buettner M, Distel L, Grabenbauer G, Young LS et al. Prognostic impact of tumour‐infiltrating Th2 and regulatory T cells in classical Hodgkin lymphoma. Hematol Oncol 2009;27:31–39. PubMed

Demehri S, Cunningham TJ, Manivasagam S, Ngo KH, Moradi Tuchayi S, Reddy R et al. Thymic stromal lymphopoietin blocks early stages of breast carcinogenesis. J Clin Invest 2016;126:1458–1470. PubMed PMC

Yue W, Lin Y, Yang X, Li B, Liu J, He R. Thymic stromal lymphopoietin (TSLP) inhibits human colon tumor growth by promoting apoptosis of tumor cells. Oncotarget 2016;7:16840–16854. PubMed PMC

Cipolat S, Hoste E, Natsuga K, Quist SR, Watt FM. Epidermal barrier defects link atopic dermatitis with altered skin cancer susceptibility. eLife 2014;3:e01888. PubMed PMC

Demehri S, Turkoz A, Manivasagam S, Yockey LJ, Turkoz M, Kopan R. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell 2012;22:494–505. PubMed PMC

Daniels TR, Leuchter RK, Quintero R, Helguera G, Rodriguez JA, Martinez‐Maza O et al. Targeting HER2/neu with a fully human IgE to harness the allergic reaction against cancer cells. Cancer Immunol Immunother 2012;61:991–1003. PubMed PMC

Daniels‐Wells TR, Helguera G, Leuchter RK, Quintero R, Kozman M, Rodriguez JA et al. A novel IgE antibody targeting the prostate‐specific antigen as a potential prostate cancer therapy. BMC Cancer 2013;13:195. PubMed PMC

Nigro EA, Brini AT, Soprana E, Ambrosi A, Dombrowicz D, Siccardi AG et al. Antitumor IgE adjuvanticity: key role of Fc epsilon RI. J Immunol 2009;183:4530–4536. PubMed

Nigro EA, Soprana E, Brini AT, Ambrosi A, Yenagi VA, Dombrowicz D et al. An antitumor cellular vaccine based on a mini‐membrane IgE. J Immunol 2012;188:103–110. PubMed

Knittelfelder R, Riemer AB, Jensen‐Jarolim E. Mimotope vaccination–from allergy to cancer. Expert Opin Biol Ther 2009;9:493–506. PubMed PMC

Fazekas J, Fürdös I, Singer J, Jensen‐Jarolim E. Why man's best friend, the dog, could also benefit from an anti‐human HER‐2 vaccine. Oncol Lett 2016;12:2271–2276. PubMed PMC

Riemer AB, Untersmayr E, Knittelfelder R, Duschl A, Pehamberger H, Zielinski CC et al. Active induction of tumor‐specific IgE antibodies by oral mimotope vaccination. Cancer Res 2007;67:3406–3411. PubMed

Lu CS, Hung AF, Lin CJ, Chen JB, Chen C, Shiung YY et al. Generating allergen‐specific human IgEs for immunoassays by employing human epsilon gene knockin mice. Allergy 2015;70:384–390. PubMed

Dodev TS, Karagiannis P, Gilbert AE, Josephs DH, Bowen H, James LK et al. A tool kit for rapid cloning and expression of recombinant antibodies. Sci Rep 2014;4:5885. PubMed PMC

Laukkanen ML, Makinen‐Kiljunen S, Isoherranen K, Haahtela T, Soderlund H, Takkinen K. Hevein‐specific recombinant IgE antibodies from human single‐chain antibody phage display libraries. J Immunol Methods 2003;278:271–281. PubMed

Hecker J, Diethers A, Etzold S, Seismann H, Michel Y, Plum M et al. Generation and epitope analysis of human monoclonal antibody isotypes with specificity for the Timothy grass major allergen Phl p 5a. Mol Immunol 2011;48:1236–1244. PubMed

Plomp R, Hensbergen PJ, Rombouts Y, Zauner G, Dragan I, Koeleman CA et al. Site‐specific N‐glycosylation analysis of human immunoglobulin E. J Proteome Res 2014;13:536–546. PubMed

Shade KT, Platzer B, Washburn N, Mani V, Bartsch YC, Conroy M et al. A single glycan on IgE is indispensable for initiation of anaphylaxis. J Exp Med 2015;212:457–467. PubMed PMC

Niki T, Tsutsui S, Hirose S, Aradono S, Sugimoto Y, Takeshita K et al. Galectin‐9 is a high affinity IgE‐binding lectin with anti‐allergic effect by blocking IgE‐antigen complex formation. J Biol Chem 2009;284:32344–32352. PubMed PMC

Josephs DH, Spicer JF, Karagiannis P, Gould HJ, Karagiannis SN. IgE immunotherapy: a novel concept with promise for the treatment of cancer. mAbs 2014;6:54–72. PubMed PMC

Karagiannis SN, Nestle OF, Gould HJ. IgE interacts with potent effector cells against tumors: ADCC and ADCP In: Penichet MJ, Jensen‐Jarolim E, editors. Cancer and IgE: introducing the concept of AllergoOncology. Springer International Publishing AG, 2010: 185–213.

Karagiannis P, Singer J, Hunt J, Gan SK, Rudman SM, Mechtcheriakova D et al. Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu‐positive tumour cells. Cancer Immunol Immunother 2009;58:915–930. PubMed PMC

Spillner E, Plum M, Blank S, Miehe M, Singer J, Braren I. Recombinant IgE antibody engineering to target EGFR. Cancer Immunol Immunother 2012;61:1565–1573. PubMed PMC

Bracher M, Gould HJ, Sutton BJ, Dombrowicz D, Karagiannis SN. Three‐colour flow cytometric method to measure antibody‐dependent tumour cell killing by cytotoxicity and phagocytosis. J Immunol Methods 2007;323:160–171. PubMed

Rudman SM, Josephs DH, Cambrook H, Karagiannis P, Gilbert AE, Dodev T et al. Harnessing engineered antibodies of the IgE class to combat malignancy: initial assessment of FcvarepsilonRI‐mediated basophil activation by a tumour‐specific IgE antibody to evaluate the risk of type I hypersensitivity. Clin Exp Allergy 2011;41:1400–1413. PubMed

Jensen‐Jarolim E, Mechtcheriakova D, Pali‐Schoell I. The targets of IgE: allergen‐associated and tumor‐associated molecular patterns In: Penichet ML, Jensen‐Jarolim E, editors. Cancer and IgE: introducing the concept of AllergoOncology. Springer International Publishing AG, 2010: 231–254.

Singer J, Jensen‐Jarolim E. IgE‐based immunotherapy of cancer: challenges and chances. Allergy 2014;69:137–149. PubMed PMC

Josephs DH, Bax HJ, Lentfer H, Selkirk C, Spicer JF, Karagiannis SN. Potential for monocyte recruitment by IgE immunotherapy for cancer in a rat model of tumour metastasis. Lancet 2015;385:S53. PubMed

Daniels TR, Martinez‐Maza O, Penichet ML. Animal models for IgE‐meditated cancer immunotherapy. Cancer Immunol Immunother 2012;61:1535–1546. PubMed PMC

Gould HJ, Mackay GA, Karagiannis SN, O'Toole CM, Marsh PJ, Daniel BE et al. Comparison of IgE and IgG antibody‐dependent cytotoxicity in vitro and in a SCID mouse xenograft model of ovarian carcinoma. Eur J Immunol 1999;29:3527–3537. PubMed

Dombrowicz D, Brini AT, Flamand V, Hicks E, Snouwaert JN, Kinet JP et al. Anaphylaxis mediated through a humanized high affinity IgE receptor. J Immunol 1996;157:1645–1651. PubMed

Dombrowicz D, Lin S, Flamand V, Brini AT, Koller BH, Kinet JP. Allergy‐associated FcRbeta is a molecular amplifier of IgE‐ and IgG‐mediated in vivo responses. Immunity 1998;8:517–529. PubMed

Fung‐Leung WP, De Sousa‐Hitzler J, Ishaque A, Zhou L, Pang J, Ngo K et al. Transgenic mice expressing the human high‐affinity immunoglobulin (Ig) E receptor alpha chain respond to human IgE in mast cell degranulation and in allergic reactions. J Exp Med 1996;183:49–56. PubMed PMC

Karagiannis SN, Bracher MG, Beavil RL, Beavil AJ, Hunt J, McCloskey N et al. Role of IgE receptors in IgE antibody‐dependent cytotoxicity and phagocytosis of ovarian tumor cells by human monocytic cells. Cancer Immunol Immunother 2008;57:247–263. PubMed PMC

Smedegard G, Revenas B, Lundberg C, Arfors KE. Anaphylactic shock in monkeys passively sensitized with human reaginic serum. I. Hemodynamics and cardiac performance. Acta Physiol Scand 1981;111:239–247. PubMed

Saul L, Josephs DH, Cutler K, Bradwell A, Karagiannis P, Selkirk C et al. Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency. mAbs 2014;6:509–522. PubMed PMC

Warncke M, Calzascia T, Coulot M, Balke N, Touil R, Kolbinger F et al. Different adaptations of IgG effector function in human and nonhuman primates and implications for therapeutic antibody treatment. J Immunol 2012;188:4405–4411. PubMed

Singer J, Jensen‐Jarolim E. IgE‐based immunotherapy of cancer ‐a comparative oncology approach. J Carcinog Mutagen 2014;5:1000176. PubMed PMC

Hammerberg B. Canine immunoglobulin E. Vet Immunol Immunopathol 2009;132:7–12. PubMed

Singer J, Fazekas J, Wang W, Weichselbaumer M, Matz M, Mader A et al. Generation of a canine anti‐EGFR (ErbB‐1) antibody for passive immunotherapy in dog cancer patients. Mol Cancer Ther 2014;13:1777–1790. PubMed PMC

Caiado J, Venemalm L, Pereira‐Santos MC, Costa L, Barbosa MP, Castells M. Carboplatin‐, oxaliplatin‐, and cisplatin‐specific IgE: cross‐reactivity and value in the diagnosis of carboplatin and oxaliplatin allergy. J Allergy Clin Immunol Pract 2013;1:494–500. PubMed

Bonamichi‐Santos R, Castells M. Diagnoses and management of drug hypersensitivity and anaphylaxis in cancer and chronic inflammatory diseases: reactions to taxanes and monoclonal antibodies. Clin Rev Allergy Immunol 2016; doi:10.1007/s12016-016-8556-5 PubMed DOI

Castells M, Sancho‐Serra Mdel C, Simarro M. Hypersensitivity to antineoplastic agents: mechanisms and treatment with rapid desensitization. Cancer Immunol Immunother 2012;61:1575–1584. PubMed PMC

Hong DI, Bankova L, Cahill KN, Kyin T, Castells MC. Allergy to monoclonal antibodies: cutting‐edge desensitization methods for cutting‐edge therapies. Expert Rev Clin Immunol 2012;8:43–52. PubMed

Banerji A, Lax T, Guyer A, Hurwitz S, Camargo CA Jr, Long AA. Management of hypersensitivity reactions to Carboplatin and Paclitaxel in an outpatient oncology infusion center: a 5‐year review. J Allergy Clin Immunol Pract 2014;2:428–433. PubMed

Raisch DW, Campbell W, Garg V, Qureshi ZP, Bookstaver PB, Norris LB et al. Description of anaphylactic reactions to paclitaxel and docetaxel reported to the FDA, with a focus on the role of premedication. Expert Opin Drug Saf 2011;10:521–528. PubMed

Joint Task Force on Practice P, American Academy of Allergy A, Immunology, American College of Allergy A, Immunology, Joint Council of Allergy A et al. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol 2010;105:259–273. PubMed

Brennan PJ, Rodriguez Bouza T, Hsu FI, Sloane DE, Castells MC. Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment. J Allergy Clin Immunol 2009;124:1259–1266. PubMed

Picard M, Pur L, Caiado J, Giavina‐Bianchi P, Galvao VR, Berlin ST et al. Risk stratification and skin testing to guide re‐exposure in taxane‐induced hypersensitivity reactions. J Allergy Clin Immunol 2016;137:1154–1164. PubMed

Kadoyama K, Kuwahara A, Yamamori M, Brown JB, Sakaeda T, Okuno Y. Hypersensitivity reactions to anticancer agents: data mining of the public version of the FDA adverse event reporting system, AERS. J Exp Clin Cancer Res 2011;30:93. PubMed PMC

Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI et al. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol 2008;122:574–580. PubMed

Cernadas JR, Brockow K, Romano A, Aberer W, Torres MJ, Bircher A et al. General considerations on rapid desensitization for drug hypersensitivity – a consensus statement. Allergy 2010;65:1357–1366. PubMed

Sancho‐Serra Mdel C, Simarro M, Castells M. Rapid IgE desensitization is antigen specific and impairs early and late mast cell responses targeting FcepsilonRI internalization. Eur J Immunol 2011;41:1004–1013. PubMed

Hsu Blatman KS, Castells MC. Desensitizations for chemotherapy and monoclonal antibodies: indications and outcomes. Curr Allergy Asthma Rep 2014;14:453. PubMed

Galvao VR, Castells MC. Hypersensitivity to biological agents‐updated diagnosis, management, and treatment. J Allergy Clin Immunol Pract 2015;3:175–185. PubMed

Sloane D, Govindarajulu U, Harrow‐Mortelliti J, Barry W, Hsu FI, Hong D et al. Safety, costs, and efficacy of rapid drug desensitizations to chemotherapy and monoclonal antibodies. J Allergy Clin Immunol Pract 2016;4:497–504. PubMed

Long A, Rahmaoui A, Rothman KJ, Guinan E, Eisner M, Bradley MS et al. Incidence of malignancy in patients with moderate‐to‐severe asthma treated with or without omalizumab. J Allergy Clin Immunol 2014;134:560–567. PubMed

Karagiannis P, Gilbert AE, Nestle FO, Karagiannis SN. IgG4 antibodies and cancer‐associated inflammation: insights into a novel mechanism of immune escape. Oncoimmunology 2013;2:e24889. PubMed PMC

AllergoOncology: Opposite outcomes of immune tolerance in allergy and cancer

Janus-faced Acrolein prevents allergy but accelerates tumor growth by promoting immunoregulatory Foxp3+ cells: Mouse model for passive respiratory exposure