Natural Killer Cell Therapy Combined with Probiotic Bacteria Supplementation Restores Bone Integrity in Cancer by Promoting IFN-γ Production

This study found a strong link between interferon-gamma (IFN-γ) secretion from immune cells and changes in bone quality in pancreatic tumor-bearing humanized-BLT (hu-BLT) mice. Tumor presence in hu-BLT mice led to bone resorption and reduced IFN-γ production compared to healthy mice. Interestingly, oral supplementation with probiotic bacteria AJ2, either alone or combined with supercharged NK (sNK) cells, inhibited tumor growth and increased IFN-γ levels in tissue compartments and tumor sites. Enhanced IFN-γ secretion was observed in cell cultures from the pancreas, spleen, PBMCs, splenocyte-derived NK cells, and bone marrow of mice treated with sNK cells and AJ2 compared to untreated tumor-bearing mice. Higher IFN-γ levels were associated with improved bone integrity in hu-BLT mice. TRAP staining showed increased osteoclastic activity and bone resorption in untreated tumor mice, in contrast to those treated with sNK and AJ2. This research highlights the role of immune cell-derived IFN-γ in preventing tumor-induced bone loss and improving bone quality, suggesting that probiotics, alone or with immunotherapies, have potential as treatments for osteolytic cancers.