Grant: Project Grant

Colorectal cancer is the third most common cancer afflicting Canadians. Cancer cells arise when the body's own cells become mutated to the point that they develop independence from the body's normal growth control mechanisms. In many cases, mutations in a gene mean that it cannot function normally. Mutations in many different types of genes can lead to colorectal cancer and some of the most common mutations change the ability of a cell to keep its DNA healthy. When this happens, cancer cells cannot repair damage to their genes and so even more faulty and abnormal-looking proteins build up inside of them. The body possesses a natural defense (the immune system) that detects and attacks foreign looking cells such as bacteria and viruses. While this system expertly recognizes and destroys infecting microbes, it consistently fails to recognize mutated cancer cells as dangerous despite their high content of abnormal proteins. Scientists are still trying to understand why this is the case and how we can help the immune system "see" cancer cells as foreign. In the proposed project, we will investigate how one immune cell type known as DCs help to alert the immune system as a whole to the presence of abnormal tumor proteins. By doing this, we think DCs regulate how likely a tumor is to be destroyed by other immune cells. We will specifically investigate if the type of colorectal cancer that is worst at repairing DNA is the most likely to attract DCs, which in turn can help activate "T cells" capable of killing the tumor cells once they see them. We think that in most colorectal cancers, DCs never come to the tumor and so T cells cannot be activated. By studying the cancers that do recruit DCs, we hope to learn how they do this to develop treatments that attract DCs to other types of colorectal cancer so that T cells can see and kill them.