The pivotal role of the epithelial barrier in mucosal tumor immunology

The mucosal epithelial barrier sits at the crossroads of immunity and tissue homeostasis, acting as both a physical defense and a sophisticated communicator between the host and the external world. This interface, once thought to be merely a passive shield, is now understood as a dynamic structure comprising epithelial cells, resident immune populations, stromal support, and the microbiome. Under normal conditions, coordinated signaling across this barrier maintains equilibrium, ensuring prompt responses to threats while promoting tolerance to innocuous antigens. However, during oncogenesis, these harmonious interactions unravel. The malignant transformation of the epithelium not only disrupts barrier integrity but also reprograms its signaling capacity, generating a microenvironment that favors tumor growth, subverts immune surveillance, and facilitates dissemination. Despite advances in immunotherapy and molecular profiling, fundamental questions remain about how epithelial barrier breakdown fuels carcinogenesis and hinders effective immune response. Deeper insights are needed to translate emerging knowledge on barrier biology into actionable strategies in mucosal cancers, which are major contributors to global cancer burden.This Research Topic aims to untangle the complex interplay between the mucosal epithelial barrier and the evolving immune microenvironment during tumor initiation, progression, and metastasis. The primary objective is to elucidate how aberrations in barrier function and adaptive epithelial remodeling orchestrate immune evasion, re-educate local and recruited immune cell populations, and condition the adjacent stromal and microbial milieu. Of particular interest are mechanistic studies that move beyond correlative observations—leveraging technologies such as organotypic cultures, spatial transcriptomics, high-resolution in vivo imaging, and gnotobiotic models—to establish causal relationships and identify novel checkpoints at this interface. Ultimately, the goal is to identify exploitable points of vulnerability for therapeutic intervention, to boost immunotherapeutic efficacy, restore immune competence, and prevent malignant transformation or metastasis.This Research Topic encompasses basic, translational, and clinical research addressing the transformation of the mucosal epithelial barrier in cancer. We seek contributions that delineate the evolution from a protective, homeostatic barrier to a pro-tumorigenic, immune-modulating interface, but are not limited to:• Mechanisms of immune homeostasis versus barrier subversion during tumorigenesis• Epithelial-derived cytokines, chemokines, lipid mediators, and extracellular vesicles shaping the immune landscape• Crosstalk among epithelial, stromal, and neural elements in tumor-driven microenvironmental remodeling• Microbiota and pathobiont influences on epithelial signaling and antitumor immunity• Comparative analyses of barrier-immune interactions across distinct mucosal tissues (e.g., lung, gut, reproductive tract)• Therapeutic strategies to enhance barrier repair, modulate epithelial signals, or target the tumor-immune-stromal-microbial interfacePlease note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.Please note that Dr. Runzhe Chen is currently employed by BeOne Medicines and holds stock options in BeOne Medicines. Topic editors: Mei Luo, Regina Chen Source: https://www.frontiersin.org/research-topics/77428/the-pivotal-role-of-the-epithelial-barrier-in-mucosal-tumor-immunology