Time-course analysis of SHIP-1 modulation and expression in a pancreatic cancer model Purchased

Pancreatic cancer (PC) is an aggressive disease with minimally effective therapies due to immunosuppression. Src Homology Inositol Phosphatase (SHIP-1) expression is essential in regulating myeloid derived suppressor cell (MDSC) and T regulatory cell (Treg) homeostasis and function, which can positively or negatively impact antitumor immunity. Inflammatory factors play an important role in the regulation of SHIP-1 expression. We demonstrated in our pancreatic cancer tumor bearing mice (TB) that SHIP-1 gene and protein expression is diminished in lymphoid tissues, correlating with an expansion of MDSC and Treg percentages compared to control mice (CTRL). These TB mice are generated via subcutaneous injection with Panc02 cells. Furthermore, we showed that inflammatory factors were elevated in TB mice compared to CTRL mice. In this study we sought to pinpoint the exact time when SHIP-1 expression was reduced, in correlation with the expansion of MDSC and Treg, along with the increase in production of inflammatory factors in TB mice. To evaluate the loss of SHIP-1, weekly time-course experiments were performed via collection of peripheral blood (PB) and lymphoid tissues for a total of 4 weeks. Preliminary data indicates a reduction of SHIP-1 expression two weeks post tumor inoculation, which correlated with the expansion of MDSC and Treg percentages and an increase in tumor and spleen weights in TB mice compared to CTRL mice. Also, PB from TB mice showed a weekly increase in the production of inflammatory factors compared to CTRL mice. The results from this study may further establish SHIP-1 as a potential therapeutic target that may help combat PC in humans.