Assessing the magnitude of immunogenic cell death following chemotherapy and irradiation reveals a new strategy to treat pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) continues to have a dismal prognosis in part due to ineffective treatment strategies. The efficacy of some chemotherapies and especially radiotherapy are mediated partially by the immune system. Therefore, we hypothesized that profiling the immune response following chemotherapy and/or irradiation can be used as a readout for treatment efficacy, but also to help identify optimal therapeutic schedules for PDAC. Using murine models of PDAC, we demonstrated that concurrent administration of stereotactic body radiotherapy (SBRT) and a modified dose of FOLFIRINOX (mFX) resulted in superior tumor control when compared to single or sequential treatment groups. Importantly, this combined treatment schedule enhanced the magnitude of immunogenic cell death, which in turn amplified tumor antigen presentation by dendritic cells and intratumoral CD8+ T cell infiltration. Concurrent therapy also resulted in systemic immunity contributing to the control of established metastases. These findings provide rationale for pursuing concurrent treatment schedules of SBRT with mFX in PDAC.