Work

Bone metastases at the nutrition–bone–immune interface: implications for immune checkpoint blockade

Year: 2026

Type: article

Abstract: Bone metastases develop within a mineralized and hematopoietic environment shaped by continuous skeletal remodeling, immune-cell trafficking, and systemic host physiology. This specialized niche can restrict immune checkpoint blockade, but the factors governing its responsiveness remain incompletely defined. Evidence linking nutritional status and related endocrine or metabolic factors to bone-specific immunity is fragmented across osteoimmunology, tumor immunology, nutrition, endocrinology, and translational oncology. We distinguish direct nutritional exposures from host-state indices, mineral endocrine regulators, and microbiome-derived metabolites. Mechanistic studies identify osteoclast-associated pathways, including RANK–RANKL signaling and osteopontin, as direct links between skeletal remodeling, impaired T-cell recruitment, and experimental resistance to checkpoint blockade. By contrast, albumin-based indices, cachexia, anemia-related measures, glucocorticoid exposure, thyroid dysfunction, and microbiome features generally provide prognostic, treatment-related, or associative evidence across heterogeneous cancer cohorts. They do not establish ICI-specific prediction, causal reversibility, or therapeutic benefit. Clinical evidence for combining checkpoint inhibitors with antiresorptive, nutritional, endocrine, or microbiome interventions remains inconsistent or preliminary. We therefore use the nutrition–bone–immune axis as a conceptual, evidence-organizing framework, not as a clinically validated unified causal pathway. Clinical translation will require prospective bone-specific cohorts, paired systemic and lesion-level profiling, rigorous temporal definitions, treatment-interaction analyses, and randomized trials integrating skeletal, immune, and oncological endpoints.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1982392

Authors: Wenshuo Liu, Tianqing Shui, Jiaqi Zhao, Lei Li

Institutions: Sheng Jing Hospital, First Hospital of China Medical University, China Medical University, China Medical University

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801