Nutritional Modulation of the Immuno–Biomineral Interface: From Vascular Calcification to a Hypothesis-Generating Framework for Tumor-Associated Biomineralization

Pathological biomineralization is increasingly recognized as a regulated biological process involving interactions among mineral metabolism, inflammation, cellular stress, extracellular vesicles (EVs), extracellular matrix (ECM) components, and mineral precursors. These processes are particularly well characterized in vascular calcification, where immune, metabolic, vesicular, and matrix-associated pathways contribute to ectopic mineral deposition. Tumor-associated mineralization is also documented in several malignancies, but its cellular origins, mineral composition, and biological significance remain substantially less defined. The Immuno–Biomineral Interface (IBI) is proposed here as a hypothesis-generating conceptual framework for integrating these interacting processes and examining potential mechanistic connections between established vascular calcification pathways and tumor-associated biomineralization. Nutritional status can modulateseveral biological processes implicated in pathological calcification, including mineral homeostasis, inflammatory signaling, oxidative stress, ECM remodeling, and EV biology. Magnesium, vitamin K2, omega-3 fatty acids, and selected polyphenols have been investigated in experimental and clinical contexts, although the strength and consistency of evidence vary according to nutrient, dose, biological system, and outcome. The strongest evidence for nutritional modulation of pathological calcification derives from vascular and renal contexts. These findings provide a mechanistic basis for considering nutrition as a potentially modifiable influence on IBI-associated processes, rather than as a single upstream determinant of pathological biomineralization. Most mechanistic evidence reviewed here derives from vascular calcification. Tumor microenvironments nevertheless exhibit processes also implicated in pathological calcification, including chronic inflammation, ECM remodeling, altered calcium and mineral handling, cellular stress, and EV-mediated communication. These observations identify potential points of mechanistic convergence but do not demonstrate that vascular and tumor-associated mineralization arise through equivalent pathways. Importantly, direct evidence that defined nutritional exposures modify the initiation, composition, maturation, or spatial distribution of tumor-associated mineral deposits remains scarce. The proposed nutrition–IBI–tumor biomineralization relationship should therefore be regarded as a testable, hypothesis-generating model rather than an established causal pathway. Asa narrative review, we integrate evidence from nutritional science, vascular biology, immunology, EV research, mineral metabolism, and cancer biology to critically distinguish established mechanisms from indirect evidence and hypothesis-generating extrapolations. We further highlight key knowledge gaps concerning nutrient-dependent regulation of immune responses, EV biology, matrix remodeling, and mineral formation within tumor microenvironments. Future studies combining defined nutritional interventions with spatial molecular profiling, EV characterization, high-resolution mineral characterization, and quantitative pathology will be required to determine whether mechanisms established in vascular calcification extend to tumor-associated biomineralization. The principal value of the IBI framework is therefore to organize existing evidence and define experimentally testable relationships between nutrition, pathological mineralization, and tumor biology while maintaining clear boundaries between established and unvalidated mechanisms.