6. Conclusion
In this Position Paper, we review recent advances in allergy and glioma heterogeneity, underlining innovative opportunities for translational research. Future epidemiological AllergoOncology research could capitalise upon modern atopy-related biomarkers for assessment in glioma development and clinical outcomes and potentially elucidate underlying molecular and cellular mechanisms. Efforts to systematically record real-world and novel biomarkers relevant to allergy and cancer risk are needed, including in cohorts, registries and in medical records. Collecting atopy-related data for monitoring immunosuppression-related changes in cancer patients is also needed. Relevant studies accounting for immune system heterogeneity, glioma diversity, and specific allergic conditions may provide improved insights into the complex allergy-glioma relationship.
BOXES
Box 1: Allergic inflammation and brain physiology
· The Blood-Brain Barrier (BBB) is no longer the only specialized border contributing to controlling neuro-immune crosstalk and brain immunosurveillance (Figure 4).87
· Similar roles have recently been attributed to the circumventricular organs (CVO), skull bone marrow channels, the meningeal lymphatic system, choroid plexus, cribriform plate and more recently the subarachnoid lymphatic-like membrane (SLYM).158
· In these structures, blood-borne resident immune cells create specialized immune niches involved in brain development, homeostasis, and protection.
· Immune cells associated with T2-immunity, such as MCs, ILC2, B-cells, and Th2-cells, can be found in these barriers.159
· IL-33, IL-13, and IL-4, which are T2-immunity related soluble factors, play a role in immune-related mechanisms associated with neuroprotection and neuroinflammation159, such as modulating synaptic remodelling and activity.160,161
· Existing evidence suggests that peripheral allergic inflammation affects brain homeostasis (Figure 5).162
· Allergic sensitization in rodent models leads to rapid activation of neuronal pathways163,164, as well as Th1- and Th2-related gene expression165,166, and accumulation of IgG and IgE in the brain parenchyma.167,168
· Studies have shown that peripheral allergic inflammation in mouse models can activate microglia into a pro-inflammatory state induced with either timothy grass pollen169, ovalbumin170, fungal allergens171 or house dust mite.151
· Mice with asthma or AD demonstrate increased activation of microglia and astrocytes in the spinal cord.170
· Epigenetic changes have been detected in microglia obtained from the offspring of mothers with allergic asthma.172
· Emerging studies are investigating differences in brain activity between allergic and non-allergic individuals.173,174
BOX 2: Research questions for new studies in allergy and glioma risk, prognosis, and treatment
· What are the most relevant and promising new allergy biomarkers for future AllergoOncology studies in glioma?
· What is the most relevant allergic phenotype, genotype, or endotype for glioma?
· Is the association of allergy and glioma most relevant for a specific glioma subtype?
· What is the association of allergy and glioma in large-scale prospective studies with comprehensive and objectively measured allergy biomarkers across the lifecourse using both systematic and agnostic analysis methods?
· Are tIgE and/or sIgE involved in glioma immunosurveillance and or immunoediting? What are the optimal threshold of IgE concentration?
· What is the association of allergy and glioma in broader geographically diverse populations with different genetic backgrounds and environmental exposures?
· What is the impact of climate-related changes in allergen exposure, allergy and glioma?
· What is the impact of anti-allergic therapies (including AIT), including their interactions, in allergy and glioma?
· What are the most relevant allergy biomarkers for monitoring immune-glioma interactions and treatment response?
· Can next generation AllergoOncology research develop an allergy-related immunoscore for the prediction of recurrence and/or response to therapeutics?
· How can patient records, registries, and databases capture the most relevant AllergoOncology data for future research?
· What is the impact of allergy on brain immunology in the context of glioma?
· Does the phenomenon of trained immunity, which is associated with the initiation of allergic diseases or influenced by allergic responses, exhibit a distinguishable and specific role in the process of glioma elimination? Can improved allergy and glioma therapeutic options be developed based on findings in AllergoOncology?
Is research and knowledge of allergic disorders and glioma relevant to other priority cancer types?