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A retrospective cohort study conducted in the UK Biobank found that individuals with allergies had a lower risk of COVID-19 infection and hospitalization in the general population. However, this association was not significant in the cancer patient population. The study suggests that allergic diseases may have immune mechanisms that help moderate the hyperinflammatory effects of COVID-19. While there was no significant association between asthma and COVID-19 diagnosis, a protective effect from COVID-19 hospitalization was observed. Further research is needed to understand the specific effects of different types of allergies and asthma on COVID-19 risk. [Extracted from the article]

The immune system interacts with many nominal 'danger' signals, endogenous danger‐associated (DAMP), exogenous pathogen (PAMP) and allergen (AAMP)‐associated molecular patterns. The immune context under which these are received can promote or prevent immune activating or inflammatory mechanisms and may orchestrate diverse immune responses in allergy and cancer. Each can act either by favouring a respective pathology or by supporting the immune response to confer protective effects, depending on acuity or chronicity. In this Position Paper under the collective term danger signals or DAMPs, PAMPs and AAMPs, we consider their diverse roles in allergy and cancer and the connection between these in AllergoOncology. We focus on their interactions with different immune cells of the innate and adaptive immune system and how these promote immune responses with juxtaposing clinical outcomes in allergy and cancer. While danger signals present potential targets to overcome inflammatory responses in allergy, these may be reconsidered in relation to a history of allergy, chronic inflammation and autoimmunity linked to the risk of developing cancer, and with regard to clinical responses to anti‐cancer immune and targeted therapies. Cross‐disciplinary insights in AllergoOncology derived from dissecting clinical phenotypes of common danger signal pathways may improve allergy and cancer clinical outcomes. [ABSTRACT FROM AUTHOR]

Basophil activation test in cancer patient blood evaluating potential hypersensitivity to an anti-tumor IgE therapeutic candidate Keywords: basophils; BAT; IgE; MOv18; ovarian cancer EN basophils BAT IgE MOv18 ovarian cancer 1 5 5 07/29/20 20200801 NES 200801 To the Editor, Monoclonal anti-tumor IgG antibodies are used widely to treat malignancies. These include superior affinity of IgE for cognate Fc receptors and the presence in tumors of effector cell populations (eg, macrophages and mast cells) known to exert anti-tumor activities when activated by IgE. [Extracted from the article]

The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti‐ulcer medications, regulate phylogenetic variability and the quality of cross talk between innate and adaptive immune cells via mucosal and skin epithelia. More recently, microbiota and their composition have been linked to protective effects for health. Imbalance, however, has been linked to immune‐related diseases such as allergy and cancer, characterized by impaired, or exaggerated immune tolerance, respectively. In this AllergoOncology position paper, we focus on the increasing evidence defining the microbiota composition as a key determinant of immunity and immune tolerance, linked to the risk for the development of allergic and malignant diseases. We discuss novel insights into the role of microbiota in disease and patient responses to treatments in cancer and in allergy. These may highlight opportunities to improve patient outcomes with medical interventions supported through a restored microbiome. [ABSTRACT FROM AUTHOR]

Despite comprising a very small proportion of circulating blood leukocytes, basophils are potent immune effector cells. The high-affinity receptor for IgE (FcɛRI) is expressed on the basophil cell surface and powerful inflammatory mediators such as histamine, granzyme B, and cytokines are stored in dense cytoplasmic granules, ready to be secreted in response to a range of immune stimuli. Basophils play key roles in eliciting potent effector functions in allergic diseases and type 1 hypersensitivity. Beyond allergies, basophils can be recruited to tissues in chronic and autoimmune inflammation, and in response to parasitic, bacterial, and viral infections. While their activation states and functions can be influenced by Th2-biased inflammatory signals, which are also known features of several tumor types, basophils have received little attention in cancer. Here, we discuss the presence and functional significance of basophils in the circulation of cancer patients and in the tumor microenvironment (TME). Interrogating publicly available datasets, we conduct gene expression analyses to explore basophil signatures and associations with clinical outcomes in several cancers. Furthermore, we assess how basophils can be harnessed to predict hypersensitivity to cancer treatments and to monitor the desensitization of patients to oncology drugs, using assays such as the basophil activation test (BAT). [ABSTRACT FROM AUTHOR]

Simple Summary: The growing field of AllergoOncology has illustrated potential for the use of IgE in cancer immunotherapy; however, there is still much to be explored within this field, particularly surrounding the links between IgE, allergy, and cancer. Exploring such links may provide useful insights to guide novel IgE-based strategies targeting cancer. Here, we summarise the existing data on both IgE in cancer epidemiology and tumour immunosurveillance, leading to the proposal of a new hypothesis, the combinatorial hypothesis, which attempts to encapsulate the complexity of the relationship between IgE-associated immune responses with cancer; and we discuss how these insights may shape the next generation of IgE-based therapeutics. IgE, the predominant antibody class of the allergic response, is known for its roles in protecting against parasites; however, a growing body of evidence indicates a significant role for IgE and its associated effector cells in tumour immunosurveillance, highlighted by the field of AllergoOncology and the successes of the first-in-class IgE cancer therapeutic MOv18. Supporting this concept, substantial epidemiological data ascribe potential roles for IgE, allergy, and atopy in protecting against specific tumour types, with a corresponding increased cancer risk associated with IgE immunodeficiency. Here, we consider how epidemiological data in combination with functional data reveals a complex interplay of IgE and allergy with cancer, which cannot be explained solely by one of the existing conventional hypotheses. We furthermore discuss how, in turn, such data may be used to inform future therapeutic approaches, including the clinical management of different patient groups. With epidemiological findings highlighting several high-risk cancer types protected against by high IgE levels, it is possible that use of IgE-based therapeutics for a range of malignant indications may offer efficacy to complement that of established IgG-class antibodies. [ABSTRACT FROM AUTHOR]

Immunoglobulin E (IgE) antibodies are well known for their role in allergic diseases and for contributions to antiparasitic immune responses. Properties of this antibody class that mediate powerful effector functions may be redirected for the treatment of solid tumours. This has led to the rise of a new class of therapeutic antibodies to complement the armamentarium of approved tumour targeting antibodies, which to date are all IgG class. The perceived risk of type I hypersensitivity reactions following administration of IgE has necessitated particular consideration in the development of these therapeutic agents. Here, we bring together the properties of IgE antibodies pivotal to the hypothesis for superior antitumour activity compared to IgG, observations of in vitro and in vivo efficacy and mechanisms of action, and a focus on the safety considerations for this novel class of therapeutic agent. These include in vitro studies of potential hypersensitivity, selection of and observations from appropriate in vivo animal models and possible implications of the high degree of glycosylation of IgE. We also discuss the use of ex vivo predictive and monitoring clinical tools, as well as the risk mitigation steps employed in, and the preliminary outcomes from, the first-in-human clinical trial of a candidate anticancer IgE therapeutic. [ABSTRACT FROM AUTHOR]