Neoadjuvant FOLFIRINOX therapy is associated with increased effector T cells and reduced suppressor cells in pancreatic cancer patients.

Purpose FOLFIRINOX has demonstrated promising results for patients with pancreatic ductal adenocarcinoma (PDAC). Chemotherapy-induced immunogenic cell death can prime antitumor immune responses. We therefore performed high dimensional profiling of immune cell subsets in peripheral blood to evaluate the impact of FOLFIRINOX on the immune system. Experimental design Peripheral blood mononuclear cells (PBMC) were obtained from treatment-naive (n=20) and FOLFIRINOX-treated patients (n=19) with primary PDAC tumors at the time of resection. PBMC were characterized by 36 markers using mass cytometry by time of flight (CyTOF). Results Compared to treatment naive patients, FOLFIRINOX-treated patients showed distinct immune profiles, including significantly decreased inflammatory monocytes and regulatory T cells (Treg), increased Th1 cells, and decreased Th2 cells. Notably, both monocytes and Treg expressed high levels of immune suppression-associated CD39, and the total CD39+ cell population was significantly lower in FOLFIRINOX treated patients compared with untreated patients. Cellular alterations observed in responders to FOLFIRINOX included a significantly decreased frequency of Treg, an increased frequency of total CD8 T cells, and an increased frequency of CD27-Tbet+ effector/effector memory subsets of CD4 and CD8 T cells. Conclusions Our study reveals that neoadjuvant chemotherapy with FOLFIRINOX enhances effector T cells and downregulates suppressor cells. These data indicate that FOLFIRINOX neoadjuvant therapy may improve immune therapy and clinical outcome in PDAC patients.