1195PAlterations in peripheral T cell subsets, T cell activation markers and immune checkpoint molecules in advanced pancreatic cancer patients receiving FOLFIRINOX or gemcitabine + nab-paclitaxel

Background: Efforts to develop successful immunotherapeutic treatments in pancreatic cancer have failed so far. One possible strategy might be the combination of established chemotherapeutic regimens (FOLFIRINOX or gemcitabine plus nab-paclitaxel [gem/nab-pac]) with checkpoint inhibitors. The goal of the present pilot study is to provide a better understanding of alterations in the expression of T cell activation markers and immune checkpoint molecules in patients with advanced pancreatic cancer receiving FOLFIRINOX or gem/nab-pac. Methods: We conducted a prospective single-center study with selected advanced pancreatic cancer patients who received FOLFIRINOX or gem/nab-pac between 2015 and 2017. Blood samples (15 ml heparinized blood, 10 ml serum) were taken at day 1 and 30 of first-line chemotherapy. Ficoll density gradient separation was used to isolate peripheral blood mononuclear cells (PBMCs). After short-term storage at -80 °C, flow cytometry was performed using a LSR Fortessa flow cytometer (BD Biosciences). CD3+ CD4+ and CD3+ CD8+ T cell count as well as the expression of FoxP3, PD-1, CTLA4, CCR7, CD62L, CD69, Tim3 and LAG 3 on CD3+ T cells was analyzed. Results: 25 eligible patients were included in the study. Two consecutive blood samples were available for 21 of these patients (FOLFIRINOX: n = 18, gem/nab-pac: n = 3). We found a broad variability within T cell subsets and change of expression in T cell activation/immune checkpoint molecules during therapy. While the majority of patients (n = 13/21, 62%) is still in follow-up, first results indicate a correlation of an increase of FOXP3+ T cells in peripheral blood during chemotherapy and worse outcome. No correlation between increase of PD-1 on peripheral T cells and prognosis was observed. Conclusions: A comprehensive RNA based (nanostring nCounter®) analysis of intratumoral immune cell infiltration of all included patients is currently ongoing. It will provide further insights on the interplay between tumoral and peripheral (T cell) immunity during chemotherapy in advanced pancreatic cancer. Legal entity responsible for the study: Stefan Böck. Funding: Friedrich-Baur-Stiftung. Disclosure: All authors have declared no conflicts of interest.