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Pancreatic ductal adenocarcinoma ( PDAC ) is a life‐threatening disease and there is an urgent need to develop improved therapeutic approaches. The role of c‐Jun N‐terminal kinase ( JNK ) in  PDAC  stroma is not well defined even though dense desmoplastic reactions are characteristic of  PDAC  histology. We aimed to explore the role of  JNK  in  PDAC  stroma in mice. We crossed  Ptf1a   Cre/+  ; Kras   G12D/+   mice with   JNK 1   −/−   mice to generate  Ptf1a   Cre/+   ;Kras   G12D/+   ; JNK 1   −/−   (Kras; JNK 1  −/−  ) mice. Tumor weight was significantly lower in Kras; JNK 1  −/−   mice than in Kras; JNK 1 +/−  mice, whereas histopathological features were similar. We also transplanted a murine  PDAC  cell line ( mPC ) with intact  JNK 1 s.c. into  WT  and   JNK 1   −/−   mice. Tumor diameters were significantly smaller in   JNK 1   −/−   mice. Phosphorylated  JNK  (p‐ JNK ) was activated in α‐smooth muscle actin ( SMA )‐positive cells in tumor stroma, and  mPC ‐conditioned medium activated p‐ JNK  in tumor‐associated fibroblasts ( TAF )  in vitro . Relative expression of Ccl20 was downregulated in stimulated  TAF . Ccl20 is an important chemokine that promotes  CD 8 +  T‐cell infiltration by recruitment of dendritic cells, and the number of  CD 8 +  T cells was decreased in Kras; JNK 1 +/−  mice compared with Kras; JNK 1  −/−   mice. These results suggest that the cancer secretome decreases Ccl20 secretion from  TAF  by activation of  JNK , and downregulation of Ccl20 secretion might be correlated with reduction of infiltrating  CD 8 +  T cells. Therefore, we concluded that inhibition of activated  JNK  in pancreatic tumor stroma could be a potential therapeutic target to increase Ccl20 secretion from  TAF  and induce accumulation of  CD 8 +  T cells, which would be expected to enhance antitumor immunity.

c‐Jun N‐terminal kinase in pancreatic tumor stroma augments tumor development in mice