This article explores how bone metastases can hinder the effectiveness of immune checkpoint blockade (ICB) therapies in tumors located elsewhere in the body. The research highlights that osteoclasts, cells involved in bone breakdown, are conditioned by bone tumors to produce osteopontin (OPN), a protein that circulates and suppresses anti-tumor T cells in primary tumors. The study demonstrates that targeting these osteoclasts or OPN can successfully restore sensitivity to ICB therapy, suggesting new therapeutic strategies for patients with bone metastases. Clinical data supports these findings, showing that denosumab, a RANKL-blocking antibody, improves ICB outcomes in these patients, unlike bisphosphonates. The article concludes that OPN levels could serve as a biomarker for predicting ICB treatment prognosis in individuals with bone metastasis.

References:

• Cheng J N, Jin Z, Su C, et al. Bone metastases diminish extraosseous response to checkpoint blockade immunotherapy through osteopontin-producing osteoclasts[J]. Cancer Cell, 2025, 43(6): 1093-1107. e9.