Human lung cancer is the leading cause of cancer death worldwide.Bevacizumab,a mAb against vascular endothelial growth factor (VEGF),in combination with chemotherapy showed significant therapeutic efficacy in human lung cancer patients.However,increased adverse effects limit its clinical utilization.Previous studies demonstrated that polysaccharide β-glucan significantly augments anti-tumor mAb-mediated efficacy via stimulation of the innate effector neutrophil complement receptor 3 (CR3).Here,we explored combined 1β-glucan with bevacizumab therapy for human lung cancer using murine xenograft models.To that end,human lung adenocarcinomas were screened for membrane-bound VEGF expression.Both subcutaneous and orthotopic lung cancer xenografi models were used to evaluate the combination therapy.We found that PC 14PE6 adenocarcinoma cells express membrane-bound VEGF both in vitro and in vivo.Bevacizumab bound to surface VEGF on PC14PE6 cells and activated complement.In the subcutaneous PC 14PE6 tumor model,β-glucan plus bevacizumab showed augmented efficacy in terms of tumor progression and long-term survival compared to bevacizumab-treated alone.These effects were accompanied with massive complement deposition and neutrophil infiltration within tumors.However,this effect was not observed in surface-bound VEGF-negative human lung tumors.Therapeutic efficacy of β-glucan with bevacizumab was further demonstrated in an orthotopic lung cancer model.Thus,our data suggest that β-glucan enhances bevacizumab-mediated efficacy and may provide therapeutic benefits for lung cancers with membrane-bound VEGF expression.