Obesity acclerates pancreatic tumor growth and increases the accummulation of myeloid derived suppressor cells

Abstract

Obesity increases the risk of several solid tumors, including pancreatic cancer. One mechanism underlying the obesity‐induced increase in tumor incidence may be an obesity‐induced increase in tumor‐derived immunosuppressive factors. Thus, the goal of the current study was to evaluate the effect of diet‐induced obesity on pancreatic tumor growth, survival and the emergence of myeloid derived suppressor cells (MDSC). MDSC inhibit anti‐tumor immunity, and expand significantly as a result of numerous tumor‐derived inflammatory signals commonly elevated in obesity. C57BL/6 mice (n=8/gr) were fed either a 30% calorie restricted diet; a 10% kcal from fat diet fed ad libitum; or a 60% kcal from fat diet fed ad libitum to generate lean, control and obese mice, respectively. Mice were injected with 1 ×106 Panc02 pancreatic tumor cells after 8 weeks on each diet. Obese mice had significantly greater tumor volumes beginning at day 25 post‐tumor implantation (P<0.05), and reduced median survival as compared to lean animals (77.5 vs. 61.5 days; P<0.05). Obese mice also accumulated significantly greater number of MDSC in the spleen as compared to lean animals (87.7± 50.5 ×106 vs. 25±3.5 ×106;P<0.05). These results demonstrate that obesity accelerates pancreatic tumor growth concurrently with an increase in immunosuppressive MDSCs. Future studies will explore possible mediators of obesity‐induced MDSC accumulation.Grant Funding Source: Pennsylvania State University Internal Funding