This paper investigates the role of immature neutrophils in bone metastases, a form of cancer that is notoriously resistant to immune checkpoint blockade (ICB) therapy. The research highlights that the protein DKK1 is instrumental in promoting an immature and immunosuppressive state in neutrophils. Furthermore, the study identifies the DKK1-CKAP4-CHI3L3 signaling pathway as a key mechanism through which these immature neutrophils inhibit anti-tumor immunity. Crucially, the authors demonstrate that blocking DKK1 can induce neutrophil maturation, thereby reducing tumor burden and significantly enhancing the effectiveness of ICB therapy in bone metastases, suggesting a promising new therapeutic strategy.

References:

• Shi T, Liu W, Luo Y, et al. CHI3L3+ immature neutrophils inhibit anti-tumor immunity and impede immune checkpoint blockade therapy in bone metastases[J]. Cancer Cell, 2025.