Use of gemcitabine- (Gem) and fluropyrimidine (FP)-based chemotherapy to reduce myeloid-derived suppressor cells (MDSCs) in pancreatic (PC) and esophagogastric cancer (EGC).

Abstract

2588 Background: Pre-clinical data demonstrates that Gem and FP treatment leads to substantial falls in MDSCs in murine cancer models. We prospectively evaluated whether such a phenomena occurs in patients (pts) with cancers treated with these agents. Methods: Peripheral blood was collected from pancreatic and esophago-gastric cancer pts prior to and following Gem or FP based therapy. PBMC was harvested with subsequent flow-cytometric analysis of HLADR- Linlow/- CD33+ CD11b+ MDSCs. Percentage change in MDSC value was compared to independent evaluation of tumor volume percentage change, measured using the RECIST v1.1 criteria for target lesion assessment. Results: 16 PC pts receiving Gem based treatment and 23 EGC pts treated with FP based therapy were analyzed. There was a statistically significant reduction in pre and post treatment MDSC % (p<0.0001). Of the 21 pts having a >10% decrease in tumor volume, 20 had a fall in MDSCs, 60% of whom the MDSCs fell by >30%. There was a statistically significant reduction in MDSC % in the remaining 18 pts who had a ≤10% decrease in tumor volume or progressive disease (p=0.0016). 4 of 7 pts with a 0-10% tumor volume decrease had a >25% fall in MDSCs. None of the 11 pts with an increase in tumor volume had a >8% increase in MDSCs. Of these, 3 pts had substantial falls in MDSCs >30%, including an EGC pt where MDSCs fell from a value above the upper limit of normal (ULN) (defined by controls, n=47), to within the normal range. In all pts with initial MDSCs above the ULN, Gem or FP therapy reduced MDSCs to within normal range, independent of response. Conclusions: Gem and FP therapy significantly reduces or stabilizes MDSCs in PC and EGC, independent of response. These findings have important significance for programs integrating chemotherapy with immunotherapies such as cancer vaccines.