2018 Grantee: Michael Curran, PhD
MD Anderson Cancer Center
Research Project: Pro-Inflammatory Conversion of the PDAC Microenvironment
Award: 2018 Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2018 – June 30, 2020
Dr. Curran is an associate professor of immunology at MD Anderson Cancer Center in Houston. He earned his PhD in immunology from Stanford University and then completed postdoctoral training at University of California, Berkeley, and Memorial Sloan Kettering Cancer Center.
As a fellow in the lab of Dr. Jim Allison, a pioneer in cancer immunotherapy, Dr. Curran was the first to describe the potential therapeutic benefits of blocking two ways that cancer cells hide from the immune system. Dr. Curran’s lab at MD Anderson focuses on studying how tumors evade and suppress the patient’s immune system. The lab looks at multiple ways to address these obstacles in immunotherapyresistant cancers, such as pancreatic and prostate cancers and glioblastoma.
While immunotherapy is effective in treating other cancer types, pancreatic cancer responds poorly, if at all, to the treatment. Unlike these more susceptible cancers, pancreatic tumors encase themselves in a “microenvironment” that contains, among many other cell types, a certain type of myeloid cells. These cells are highly immunosuppressive, shielding the cancer cells from immune recognition or attack. The cells are thought to prevent immunotherapeutic strategies, developed by Dr. Curran and colleagues, that have been effective in other cancer types from working for pancreatic cancer patients.
In addition to the kind of myeloid cells described above, there are other types of myeloid cells, known as dendritic cells, that are needed to trigger the immune system to attack the cancer cells. However, dendritic cells are almost absent from pancreatic tumors and their microenvironment.
Myeloid cells can recognize pieces of DNA that are incorrectly inside cells in the cytoplasm, instead of in the nucleus. The Stimulator of Interferon Genes (STING) pathway senses this error and triggers an immune response to attack it.
Dr. Curran and his research team have created exceptionally potent drugs to activate the STING pathway. They propose to study the ability of these STING activators to change the pancreatic cancer myeloid microenvironment from an immune-suppressive site to an immune-supportive site.
Additionally, the investigators’ preliminary studies have shown that the lack of dendritic cells in these tumors is a major factor in limiting their response to STING activators and to immune therapies in general. Therefore, they propose to introduce dendritic cells specifically programmed to be attracted to, and collect in, pancreatic tumors throughout the body. This combination strategy has the potential to make pancreatic cancer vulnerable to immunotherapy. All these agents and processes are in the clinic in some form, so the time to translate any promising findings to the clinic for pancreatic cancer patients would be short.