Pancreatic cancer is a lethal disease for which most therapies have very limited success. One of the main reasons for this is the presence of a strong immunosuppressive environment around the tumor. Not only the immune system is not recognizing and attacking the tumor but it is actually suppressing it. Therefore, strategies that can reverse immunosuppression into immune activation will be key to improve treatments outcomes. To learn how to improve outcomes we actually focused on learning what is different on tumors from patients that survived pancreatic cancer long-term vs typical tumors. We found that tumors from patients who survived the disease long-term have a much more activated immun...

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Pancreatic cancer is a lethal disease for which most therapies have very limited success. One of the main reasons for this is the presence of a strong immunosuppressive environment around the tumor. Not only the immune system is not recognizing and attacking the tumor but it is actually suppressing it. Therefore, strategies that can reverse immunosuppression into immune activation will be key to improve treatments outcomes. To learn how to improve outcomes we actually focused on learning what is different on tumors from patients that survived pancreatic cancer long-term vs typical tumors. We found that tumors from patients who survived the disease long-term have a much more activated immune system to fight the cancer. Furthermore, we found that some specific bacteria is present only on tumors from long term survivors and it distinguishes the tumors from patients who succumbed to the disease in shorter time. We have found that a tumor signature made of 4 bacteria types can predict long term survivorship in patients who have surgery to remove their pancreatic cancer. Furthermore, we performed fecal microbial transplants using stools from patients with cancer, healthy controls or cancer survivors into mice with pancreatic cancer. We found that fecal transplants from survivors slowed tumor growth and increase tumor immunoactivation compared to tumors from mice transplanted with stools from pancreatic cancer patients. In this grant we aim to study the role of gut and tumor bacteria in modulating the tumor microenvironment and tumor growth. We will use bacteria extracted from tumors or specific bacteria to test their role in reversing resistance to chemotherapy or immunotherapy. Finally, we propose a small trial in patients with pancreatic cancer previous to surgery to test if we can alter the tumor microbiome and turn an inactive immune system to an activated one which can attack the tumor.

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