Hypofractionated Radiation Induced the Immunogenic Death of Bladder Cancer Cells Leading to the Immune Sensitization of Dendritic Cells

Purpose Radiotherapy is a commonly used method in the treatment of bladder cancer (BC). Radiation induced immunogenic death (ID) and antitumor immune response are related to the prognosis of radiotherapy. As the most powerful antigen-presenting cell in the body, the role of dendritic cells (DCs) is not very clear. Methods Apoptosis level, cell cycle analysis and expression levels of high mobility group protein 1 (HMGB1), calreticulin (CRT) and heat shock protein 70 (HSP70) were performed for bladder cancer cells after hypofractionated radiotherapy. The effects of the conditioned media on DCs for antitumor immune response activation were studied as well. Results The significantly increased apoptosis level, G2/M phase cell cycle arrest and significantly increased HMGB1, CRT and HSP70 expressions, and increased secretion of CCL5 and CCL21 in the supernatant of bladder cancer cells after hypofractionated radiotherapy. The expression of CD80, CD86, CCR5 and CCR7 on DCs was upregulated in the conditioned media of bladder cancer cells after hypofractionated radiotherapy. Conclusion Hypofractionated radiation blocked the cell cycle of BC cells in the G2/M phase and induced ID occurrence, resulting in DCs immune sensitization, which is of great clinical significance in understanding the radiotherapy of BC and the immunoregulation function of DCs.