Grants - Translational Grants - Texas - 2019

Florencia McAllister, M.D.

Pancreatic cancer is the 3rd leading cause of cancer-related death in the United States, with a five-year survival rate of less than 9 percent. Activation of the immune response in the microenvironment is associated with better outcomes in pancreatic cancer patients. The tumor and gut microbiota has recently been shown to influence tumor progression by modulating the tumor microenvironment.

We have recently demonstrated that the composition of the gut microbiome may determine tumor behavior and outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. We have identified specific bacteria signatures in the tumors of long-term survivors (LTS) compared to the stage-matched- short-term survivors (STS). We have also shown that transplantation of fecal microbiome from LTS or healthy controls of pancreatic cancer patients into a mouse model of PDAC significantly reduces pancreatic cancer growth. These important findings prompted us to target tumor microbiome as a therapeutic approach in pancreatic cancer patients. Here, we propose to transplant stools from PDAC long term survivals or healthy controls into PDAC patient to change their immune suppressive behavior to immunoactivated one. To this end, we will first analyze the changes in microbiome of PDAC patients after the transplantation of gut microbiome from long term survivals or health controls. Next, we will evaluate the tissue obtained from biopsy and surgical specimen for the changes in tumor microbiome of PDAC patients. Finally, we will characterize the tumor immune infiltrates from tissues obtained from PDAC patients to see if we can switch PDAC immunosuppressive TME into immunoactivated by fecal microbial transplantation. This proposal would be the stepping stone to move forward efficacy trials in PDAC patients combining FMT with standard treatment or immunotherapy.