144 Background: Chronic pancreatitis increases the risk of developing pancreatic ductal adenocarcinoma (PDAC), one of the deadliest human cancers. Activating Kras mutations have been detected in 30% of early pancreatic intraepithelial neoplasias (PanINs), increasing to 100% in PDAC. We hypothesized that inflammatory cells recruited to the pancreas in response to chronic injury can interact with epithelial cells harboring activated KrasG12D and affect the progression of PanIN lesions. Methods: We used the the transgenic Mist1:CreERT2; LSL-KrasG12D (KCiMist1) adult mice in which the LSL KrasG12Dallele is activated specifically in the acinar compartment. This model leads to the formation of PanINs with a classic "ductal" phenotype and the progression of lesions is accelerated by the induction of chronic pancreatitis with recurrent cerulein injections. Results: We have found that TH17 cells, a subtype of CD4+ T-helper cells known to play an active role in inflammation, are recruited to the pancreas during chronic pancreatitis and further increased upon KrasG12Dactivation. The differentiation of CD4+T cells into TH17 requires IL-6 and TGF-B, factors that are increased in the pancreatic tumor microenvironment. Stat3, a key transcription factor that determines the differentiation of TH17 lineage, is activated in the pancreatic dysplastic epithelium and in the stroma. We have discovered that PanINs from KCiMist1 mice overexpress the IL-17 Receptor (IL-17RA) by immunofluorescence and furthermore we confirmed this finding on human PanIN tissue arrays. Intrapancreatic injections of adenovirus encoding IL-17A, the main cytokine produced by TH17 cells, into KCiMist1 mice led to an increase in the progression of PanIN lesions by 6 weeks when compared with mice injected with control adenovirus. Finally, we transplanted IL-17-/- bone marrow into KCiMist1 mice and showed a significant decrease in metaplasia and PanINs formation when compared with mice transplanted with WT bone marrow. Conclusions: We found that TH17 cells, recruited to the pancreas in the presence of chronic pancreatitis, can accelerate the progression of early pancreatic tumorigenesis, setting the basis for future translational studies targeting TH17 cells.