Response to FOLFIRINOX neoadjuvant chemotherapy is associated with a high prevalence of Tbet expressing T cells in pancreatic cancer patients

Abstract

Abstract FOLFIRINOX is the first line treatment option for patients with pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant chemotherapy has a beneficial effect on overall survival in PDAC in comparison with upfront surgery and adjuvant therapy. However, chemotherapy has not yet been successfully combined with immune therapy in PDAC. Herein, we characterize the immunologic effect of FOLFIRINOX and thus provide a rationale for future combination with immune therapy in PDAC. Peripheral Blood Mononuclear Cells were obtained from treatment-naïve (n=20) and FOLFIRINOX-treated patients (n=15) with primary PDAC tumors. Immune cell subset composition was assessed by using mass cytometry (CyTOF). Response to FOLFIRINOX was defined as a reduction in tumor size by more than 30%. 8 of 15 patients were considered responders with a range from 32 to 60% reduction in tumor volume. Responders to FOLFIRINOX showed a significantly higher proportion of CD8+ T cells and lower proportion of monocytes in their peripheral blood compared to treatment naïve patients (both p<0.05). Responders to FOLFIRINOX treatment also showed a significantly lower percentage of CD39+ Treg cells and a significantly higher percentage of CXCR3+CCR6+ Th1/Th17 cells compared to treatment naïve patients (both p<0.05). Lastly, FOLFIRINOX responders showed significantly higher proportions of Tbet expressing CD4+ and CD8+ T cells compared to non-responder patients (both p<0.05). Taken together, our study reveals that neoadjuvant chemotherapy with FOLFIRINOX could enhance functional T cells and down-regulate suppressor cells in circulation. Thus, combination neoadjuvant FOLFIRINOX chemotherapy with immunotherapy may improve clinical outcome.