A novel radio-sensitization method for lung cancer therapy: enhanced radiosensitization induced by antigens/antibodies reaction after targeting tumor hypoxia using Bifidobacterium

Abstract Background：The hypoxic microenvironment of solid tumors reduces the susceptibility of cancer cells to radiotherapy. Current treatments are focused on the development of anti-cancer agents that selectively target tumor cells with no toxicity to healthy tissue. Bacteria colonize and destroy tumors and have emerged as biological vectors that can survive in the tumor microenvironment. Methods：In this study, a Lewis lung carcinoma transplant mouse model was established and treated with a combination of bifidobacterium infantis (Bi), its specific monoclonal antibodies (Ab) and radiotherapy (RT). 18F-FDG PET/CT and 18F-FMISO PET/CT imaging were performed to monitor tumor growth and hypoxia in the tumor tissue. Phosphorylated histone (γ-H2AX), the proliferation index (Ki-67), platelet endothelial cell adhesion molecules (CD31), tumor necrosis factor-α (TNF-α), hypoxia inducible factor-1α (HIF-1α) and glucose transporter 1 (Glut-1) levels were assessed through immunohistochemistry. Results：The results showed that the combined treatment group (Ab+ Bi+ RT) displayed delayed tumor growth and prolonged the survival of mice. The combined treatment group also had lower levels of HIF-1α, Glut-1, and CD31 expression, and a lower uptake of FDG and FMISO. The tumors treated with the combination therapy also had lower levels of hypoxia, and increased γ-H2AX and TNF-α expression. Conclusion：Taken together, these data suggest that the combination of bifidobacterium infantis and its specific monoclonal antibodies can markedly improve the efficacy of radiotherapy for the treatment of lung cancer.