Work

Bone Metastasis and the Immunosuppressive Tumor Microenvironment: Mechanisms and Therapeutic Strategies

Year: 2026

Type: review

Abstract: T-cell exhaustion, regulatory T-cell enrichment, and natural killer cell dysfunction. Transforming growth factor-β (TGF-β) released during the "tumour-bone" vicious cycle further amplifies local immunosuppression, and metabolic reprogramming depletes glucose and amino acids while accumulating lactate, directly impairing effector T-cell function. Immune checkpoint inhibitor (ICI) therapy shows limited efficacy in bone metastases; however, combination strategies including bone-protective agents (denosumab, bisphosphonates), metabolic modulators, cytokine- or extracellular vesicle-targeted agents, novel nanodelivery systems, and engineered cell therapies demonstrate encouraging preclinical and early clinical promise for reversing immunosuppression. Translation still faces major challenges, including microenvironmental heterogeneity, a lack of bone-specific biomarkers, combination-related toxicity, and delivery bottlenecks. This review aims to synthesize the mechanisms underlying the immunosuppressive bone-metastasis microenvironment and to appraise current and emerging combination strategies, thereby informing individualized treatment for patients with bone metastases.

Source: Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics

DOI: 10.32604/or.2026.090531

Authors: Minghao Ba, Yuzhu Chen, Peng Jiang, Shanshan Cai, Xin Huang, Tongmei Zhang