GRANTEE: PHILIPPE FOUBERT, PHD
Institution: University of California, San Diego
Research Project: Role of Inflammation in Pancreatic Cancer
Award: 2009 Ruth Fredman Cernea – Pancreatic Cancer Action Network – AACR Fellowship
Award Period: July 1, 2009 – June 30, 2010
Click here to download Dr. Foubert’s Grant Snapshot (pdf)
Dr. Foubert received his PhD in vascular biology and haemostasis from the Cardiovascular Research Institute, University of Paris, France, and then began postdoctoral training at the Moores Cancer Center at University of California, San Diego. His research focuses on the regulation of inflammation and anti-tumor immunity by myeloid cells (bone marrow-derived cells which infiltrate malignant tumors and promote tumor progression). Dr. Foubert’s graduate work resulted in several scientific publications and two patents. He received the 2007 Young Researcher Prize from the French Angiogenesis Network and the 2006 Diderot Innovation Prize from the University of Paris.
Recognizing that urgent need to better understand the causes and care for pancreatic cancer, Dr. Foubert has decided to contribute to efforts to improve knowledge in tumor inflammation and antitumor immunity that may lead to development of new targeted therapeutic strategies for the disease.
During the progression of pancreatic cancer, inflammatory cells rush into pancreatic tumors, cause increased tumor growth and metastasis, and stop immune cells from recognizing the tumor as a foreign body and fighting to kill them. Dendritic cells are immune system cells that can play pivotal roles in anti-tumor responses. However, as pancreatic cancer progresses, dendritic cells become unable to activate an adequate immune response toward cancer cells. Factors produced by tumor cells and inflammatory cells keep these dendritic cells in an immature state, which suppresses the activation of killer cells, allowing tumors to grow. However, it remains unclear how inflammatory cells inhibit the maturation of dendritic cells.
In this project, which is funded in memory of Ruth Fredman Cernea, Dr. Foubert plans to explore this relationship. Specifically, he plans to study the role of alpha4 integrin, an inflammatory cell adhesion molecule, in the regulation of immunosuppression during pancreatic cancer progression. To better identify the role of alpha4 integrin, he will inject pancreatic adenocarcinoma cells in the pancreas of normal and alpha 4 integrin mutant mice to analyze how inflammatory cells affect dendritic cell function in pancreatic tumors. He also will use human pancreatic tumor specimens to characterize the relative balance of myeloid cells and dendritic cells to determine if tumor inflammation can predict poor outcomes.
The study is expected to provide new insights into the mechanisms that cause tumor-induced suppression of the immune system. Since tumor inflammation promotes tumor metastasis (spread), the funded projected has important clinical significance and may also lead to the development of new therapeutic strategies to treat pancreatic cancer progression and metastasis.
Dr. Philppe Foubert talks to the staff of the Pancreatic Cancer Action Network about the immune reaction in pancreatic cancer.
Research Update from 2009 Grant Recipient, Philippe Foubert, PhD
On March 10, 2010, the Pancreatic Cancer Action Network national office was thrilled to welcome Philippe Foubert, PhD to present his exciting research. Dr. Foubert was the recipient of the Ruth Fredman Cernea – Pancreatic Cancer Action Network – AACR Fellowship in 2009. He is currently a postdoctoral fellow at the University of California, San Diego, working in the laboratory of Judith Varner, PhD.
The title of Dr. Foubert’s talk was “Role of inflammation and immunity in pancreatic cancer”. He presented background information about the complex relationship between the immune system and cancer. Over a century ago, scientists discovered immune cells intermixed with cancer cells. Dr. Foubert carefully explained the balance between the presence of immune cells that could attack the cancer and thereby benefit the patient, and those that support the growth of the tumor. A very promising research aim is to skew the balance towards the presence of cells that can kill the cancer cells.
Dr. Foubert and colleagues have determined that a protein known as alpha 4-integrin functions to recruit immune cells to the tumor that foster the growth of the tumor, to the detriment of the patient. Therefore, they have developed a mouse model that expresses a mutated (nonfunctional) version of the alpha 4-integrin protein, and implanted pancreatic tumor cells in the pancreata of these mice. Strikingly, preliminary research suggests that the absence of functional alpha 4-integrin impedes the development of pancreatic tumors, by blocking infiltration of the unfavorable immune cell types, and promoting the presence of immune cells that can fight the cancer cells. Dr. Foubert and colleagues will next investigate whether they can recapitulate these results by blocking alpha 4-integrin with a drug, with future goals to analyze this drug’s effectiveness in humans. The Pancreatic Cancer Action Network is extremely proud of the work that Dr. Foubert has accomplished during this grant term and is very optimistic about his future contributions to the field of pancreatic cancer research.