Immune perturbation in arsenic-induced adverse health effects and cancers

Abstract

Chronic exposure to inorganic arsenic remains a global health concern and is strongly associated with cutaneous malignancies, pigmentation abnormalities, internal cancers, and a range of non-malignant outcomes. In addition to direct genotoxic stress and epigenetic remodeling, arsenic exerts broad immunomodulatory effects that shape disease initiation, persistence, and progression. In the skin, arsenic perturbs barrier integrity, antigen presentation, cytokine networks, and immune surveillance—features that may contribute to the multiplicity and recurrence that characterize arsenic-associated skin cancers. Emerging evidence also highlights the importance of exposure timing (particularly perinatal windows), co-exposures, and host susceptibility factors. This review synthesizes recent advances in: (i) exposure assessment (including noninvasive image-based estimation and biomarker interpretation in the context of diet), (ii) long-latency cancer risk and the population impact of water mitigation, (iii) keratinocyte stress and inflammatory signaling pathways that intersect with cutaneous immune dysregulation, (iv) perinatal metal exposure and allergic disease trajectories with immune profiling, and (v) genetic and epigenetic determinants of susceptibility (including polymorphisms influencing tissue remodeling and arsenic metabolism). We propose an updated framework in which arsenic-driven immune perturbation acts as a unifying axis linking exposure to cutaneous carcinogenesis, internal cancers, and allergic phenotypes, and we outline research gaps and translational opportunities for precision prevention.