Deficiencies in Natural Killer Cell Numbers, Expansion, and Function at the Pre-Neoplastic Stage of Pancreatic Cancer by KRAS Mutation in the Pancreas of Obese Mice.

The combined/synergistic effect of genetic mutation of KRAS in the pancreas and obesity, a life-style factor on suppression of natural killer (NK) cells at the pre-neoplastic stage of pancreatic cancer has not been investigated and is the subject of this report. Obese mice with KRAS (KC) mutation in the pancreas fed with high-fat calorie diet (HFCD) exhibit severe deficiencies in the NK cell expansion and function at the pre-neoplastic stage of pancreatic cancer. Decreased NK cell-mediated cytotoxicity is observed in the peripheral blood, spleen, pancreas, and peri-pancreatic adipose tissue in obese KC mice, whereas in bone marrow an increased NK cell-mediated cytotoxicity is observed when compared to lean WT mice fed with control diet (CD).