Evaluation of the Synergistic Effects of Photobiomodulation and Natural Killer Cell Therapy in a Colorectal Cancer Xenograft Mouse Model

Background: Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide, highlightingthe need for more effective therapeutic approaches. This study aimed to evaluate the synergistic antitumoreffects of combining natural killer (NK) cell-based immunotherapy with photobiomodulation (PBM) in a CRCxenograft model.Methods: Human peripheral blood-derived NK cells were isolated, and their cytotoxic activity was confirmedin vitro against HT-29 CRC cells. Nude mice bearing HT-29 xenografts were assigned to four groups: control,PBM (808 nm), NK therapy, and combined NK + PBM treatment. Tumor size was monitored throughout thestudy, and excised tumors were analyzed histologically for NK cell infiltration, mitotic index, and apoptosis.Results: Both NK therapy and PBM alone significantly reduced tumor growth compared to the control. Thecombined NK + PBM group demonstrated the greatest suppression of tumor progression. Histopathologicalanalysis revealed markedly enhanced NK cell infiltration, decreased mitotic activity, and increased apoptosisin the combination group compared to the monotherapy groups.Conclusion: NK therapy and PBM each exert anti-tumor effects in CRC xenografts; however, their combinationproduces a superior therapeutic response. PBM may serve as a promising adjuvant to enhance NK-basedimmunotherapy in CRC.