Effect of triple therapy with low-dose total body irradiation and hypo-fractionated radiation plus anti-programmed cell death protein 1 blockade on abscopal antitumor immune responses in breast cancer

Immunostimulatory effects of radiotherapy can be synergistically augmented with immune checkpoint blockade to act both on irradiated tumor lesions and distant, non-irradiated tumor sites. Our hypothesis was that low-dose total body irradiation (L-TBI) combined with hypo-fractionated radiotherapy (H-RT) and anti-programmed cell death protein 1 (aPD-1) checkpoint blockade would enhance the systemic immune response. We tested the efficacy of this triple therapy (L-TBI + H-RT + aPD-1) in BALB/c mice with bilateral breast cancer xenografts. The L-TBI dose was 0.1 Gy. The primary tumor was treated with H-RT (8 Gy × 3). The PD-1 monoclonal antibody was injected intraperitoneally, and the secondary tumors not receiving H-RT were monitored for response. The triple therapy significantly delayed both primary and secondary tumor growths, improved survival rates, and reduced the number of lung metastasis lesions. It increased the activated dendritic and CD8+ T cell populations and reduced the infiltration of myeloid-derived suppressor cells in the secondary tumor microenvironment relative to other groups. Thus, L-TBI could be a potential therapeutic modality, and when combined with H-RT and aPD-1, the therapeutic effect could be enhanced significantly.