The combination of
radiotherapy and
immunotherapy may generate synergistic anti-
tumor host immune responses and promote abscopal effects. Spatial fractionation of a radiation dose has been found to promote unique physiological responses of
tumors, which might promote synergy with
immunotherapy. To determine whether spatial fractionation may augment immune activity, whole-
tumor or spatial fractionation grid
radiation treatment (GRID) alone or in combination with
antibodies against immune checkpoints PD1 and CTLA-4 were tested in an immunocompetent mouse model using a triple negative
breast tumor (4T1).
Tumor growth delay, immunohistochemistry and flow cytometry were used to characterize the effects of each treatment type. Whole-beam radiation with
immune checkpoint inhibition significantly restrained
tumor growth in the irradiated
tumor, but not abscopal
tumors, compared to either of these treatments alone. In mice that received spatially fractionated irradiation, evidence of abscopal immune responses were observed in contralateral
tumors with markedly enhanced infiltration of both antigen-presenting cells and activated T cells, which were preceded by increased systemic IFNγ production and led to eventual
tumor growth delay. These studies suggest that systemic immune activation may be triggered by employing GRID to a primary
tumor lesion, promoting anti-
tumor immune responses outside the treatment field. Interestingly, PD-L1 was found to be upregulated in abscopal
tumors from GRID-treated mice. Combined radio-
immunotherapy therapy is becoming a validated and novel approach in the treatment of
cancer. With the potential increased benefit of GRID to augment both local and metastatic disease responses, further exploration of GRID treatment as a part of current standards of care is warranted.