Low type-2 immune effectors modulate atopic diseases' protective role in pancreatic cancer risk
Studies reported that atopic individuals exhibit a 36% reduced risk of developing pancreatic ductal adenocarcinoma (PDAC); however, the underlying molecular mechanisms remain unclear. This study examines the specific role of type-2 immune response in the atopy-PDAC inverse association. To endotype a...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
| Repositorio: | r-FISABIO. Repositorio Institucional de Producción Científica |
| OAI Identifier: | oai:fisabio.fundanetsuite.com:p18559 |
| Acceso en línea: | https://fisabio.portalinvestigacion.com/publicaciones/18559 |
| Access Level: | acceso abierto |
| Palabra clave: | allergy asthma blood eosinophils pancreatic cancer serum IgE type-2 immunity |
| Sumario: | Studies reported that atopic individuals exhibit a 36% reduced risk of developing pancreatic ductal adenocarcinoma (PDAC); however, the underlying molecular mechanisms remain unclear. This study examines the specific role of type-2 immune response in the atopy-PDAC inverse association. To endotype atopic conditions using type-2 immune effectors (i.e., eosinophils and immunoglobulin-E[IgE]) and investigate their protective effect against PDAC risk, IgE levels were measured in 688 PDAC cases and 558 controls from the PanGenEU case-control study. 'IgE-sensitization' was defined as having >100 kU/L total IgE with lab-tested sensitization to >= 1 food- or aeroallergens. Atopic conditions were determined using the European Community Respiratory Health Survey questionnaire. The UK Biobank cohort's 544 PDAC cases and 92,038 nested controls were categorized based on a threshold of 0.15 x 10(9) eosinophil cells/L plus self-reported atopy. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Restricted cubic splines were applied to examine the nonlinear relationship between type-2 immune effectors and PDAC risk. PDAC risk was not linearly associated with type-2 immune effectors levels. Compared to low IgE-sensitized non-atopic individuals, the low IgE-sensitized atopic population had significantly reduced PDAC risk (OR = 0.56, 95% CI: 0.35-0.84). Similar trends were observed among atopic individuals with low eosinophil counts (OR = 0.67, 95% CI: 0.47-0.95). Atopic conditions were inversely associated with PDAC risk, particularly among those with low levels of type-2 immune effectors. This indicates the protective effect of atopy against PDAC risk is modulated by low type-2 immune response. |
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