B-Cell-Specific Antitumor Immunity Induced by PAMPs
Abstract
Metastatic breast cancer involving spread to the peritoneal cavity (the abdominal wall space) is referred to as peritoneal carcinomatosis. This form of cancer has a very poor prognosis. There is no effective way to cure this disease. We have generated preliminary data in a mouse model of breast cancer-induced peritoneal carcinomatosis that show that immune-stimulating molecules isolated from pathogens, called pathogen-associated molecular patterns (PAMPs), can treat this deadly disease. We have found that B lymphocytes -- the population of immune cells that produce antibodies -- are required for this effect. However, before a PAMP-based treatment could be applied in the clinic, it will first be necessary to understand the mechanism(s) through which this effect is obtained. Only then can a treatment be fully translated from mouse to humans. The goal of our study is to determine how PAMPs activate B cells and other immune cell types to kill tumor cells. If we do this, we will be able to develop effective therapies that can treat peritoneal carcinomatosis in humans. Thus, this application addresses the overarching challenge of reducing the mortality associated with metastatic breast cancer. We have proposed three aims that will enable us to determine how PAMPs and B lymphocytes are working. In Aim 1, we will investigate the different ways B cells inhibit tumor growth. In Aim 2, we will determine the other cell populations that are required for the anti-tumor effects and determine what cell types must first respond to the PAMPs. Finally, in Aim 3, we will determine how the complement pathway, which consists of innate soluble factors, can be activated to directly attack and kill tumor cells either in the presence or absence of B cells. Once we determine how B lymphocytes, PAMPs, and complement are working together to destroy breast cancers that have spread to the peritoneum in mice, we can start to predict and test the best ways in which to activate these anti-tumor responses in patients with peritoneal carcinomatosis. If treatments are devised to be as effective in humans as in mice, we will have made a major impact on ending breast cancer mortalities associated with metastatic spread to the peritoneal cavity and potentially other sites.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510585
Entities
People
- Karen M Haas
Organizations
- United States Army
- Wake Forest University