Food Allergy-Induced Systemic Immune Alterations Affect Tumor Progression in a CT26 Colon Adenocarcinoma Mouse Model.

Abstract

BACKGROUND: AllergoOncology has emerged as an interdisciplinary field exploring the interaction between allergic diseases and cancer; however, the lack of stable in vivo models has limited mechanistic investigations. This study aimed to establish an experimental animal model to explore the impact of systemic allergic responses on tumor progression and to provide preliminary insights into the regulatory role of allergy in cancer development. METHODS: An ovalbumin (OVA)-induced systemic allergy tumor-bearing mouse model (OVA-TM) was established by OVA sensitization followed by subcutaneous implantation of CT26 colon cancer cells. Tumor growth, immune responses, and behavioral changes were systematically evaluated. Tumor immune microenvironment alterations were assessed using immunological and histological analyses. Transcriptomic profiling and mass spectrometry imaging (MSI) were integrated to investigate immune-related metabolic alterations. Human tumor survival datasets were used to validate the prognostic relevance of differentially expressed genes (DEGs), and enrichment analyses of allergy- and cancer-associated genes were performed using humanized databases. RESULTS: OVA-induced systemic allergy significantly suppressed tumor growth and promoted immune cell infiltration, particularly CD3CD8T cells. Transcriptomic analysis identified key DEGs, including Aoc1, Apob, Apobec2, and Acta1, whose expression correlated with overall survival in multiple cancer types. Integrated transcriptomics and pathway enrichment analysis revealed extensive functional reprogramming in OVA-TM tumors, including activation of metabolic and immune-related pathways. Consistent with these findings, spatial metabolomics analysis showed synergistic alterations in lipid and amino acid-related metabolic pathways in both tumors and the spleen. CONCLUSION: This study establishes a practical in vivo model for AllergoOncology and demonstrates that systemic allergic responses can modulate tumor progression through immune activation, apoptosis, and inflammation-metabolism axis reprogramming, providing a foundation for future mechanistic and therapeutic studies.