GRANTEE: William Hawkins, MD
Washington University in St. Louis
Research Project: Targeting Tumor Infiltrating Myeloid Cells to Enhance Immunotherapy
Award: 2016 Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2016 – June 30, 2018
Since 2014, Dr. Hawkins has served as chief of the section of hepatobiliary, pancreatic and gastrointestinal surgery at Washington University in St. Louis. He is also the Neidorff Family and Robert C. Packman Professor of Surgery and program director of the Washington University Fellowship in HPB Surgery. Dr. Hawkins received his bachelor’s and medical degrees at State University of New York at Stony Brook and conducted his surgical training at Deaconess-Harvard Surgical Service, Memorial Sloan-Kettering Cancer Center and Massachusetts General Hospital. This is Dr. Hawkins’ second research grant from the Pancreatic Cancer Action Network; he also received the Skip Viragh – Career Development Award in 2005.
Working closely with other Washington University investigators, Dr. Hawkins has built a collaborative research team based on the multidisciplinary model of pairing scientists with clinicians. As a group, they have been very successful and highly cooperative. Dr. Hawkins’ own laboratory focuses on immunotherapy of pancreatic cancer in addition to molecular therapeutics.
Pancreatic tumors are characterized by a dense, complex mixture of cells, known as the stroma, which surrounds and infiltrates the tumor. The stroma is thought to protect the tumor in several ways – delivering nutrients to sustain tumor growth, creating a shield that impedes drug delivery and actively blocking an immune attack against the cancer cells.
Strategies are being tested to turn off the stroma’s ability to impede the immune system, allowing immune cells to recognize and kill the cancer cells. One approach involves the inhibition of a protein called CCR2, which is involved in the recruitment of key immune-suppressive cells to the pancreatic tumor stroma. CCR2 is a type of protein called a chemokine receptor, which binds to small proteins that activate migration, or movement, of other cells. Laboratory experiments and an early-phase clinical trial involving CCR2 inhibition (conducted primarily by another Pancreatic Cancer Action Network grant recipient, David Linehan, MD) have shown promising results. However, another chemokine receptor, called CXCR2, has been observed at increased levels in cells exposed to CCR2 inhibition, suggesting a compensatory mechanism that could allow the cancer cells to continue to “hide” from the immune system.
The current proposal builds on these observations with the hypothesis that a combinatorial approach to targeting the recruitment of immune-suppressive cells through chemokine receptor blockade will alleviate immune suppression in the stroma and promote an environment where vaccination will be most successful. Dr. Hawkins and his colleagues plan to explore the effectiveness of anti-tumor vaccination in combination with blocking CXCR2 alone, or inhibiting both CXCR2 and CCR2, in a mouse model of pancreatic cancer.