Modulating Immune Cell Glycosylation as a Strategy to Improve the Anti-Tumor Response

Cancer cells develop ways of escaping and hiding from the immune system so that they are not recognized as unhealthy cells. If our immune cells could recognize the abnormal cancer cells growing in the body they would attack and kill the cancer cells. A big problem is that we don’t know enough about how different types of immune cells regulate their response to tumor cells; so we don’t how to manipulate the system to get the immune cells to engage and attack the tumor. One way that immune cells regulate their response to tumor cells is through the binding of sugars, called glycans. Glycans on immune cells and on tumor cells have been shown to be critical in the regulation of the anti-tumor immune response. Recently, we discovered unique glycan on immune cells in the breast tumor microenvironment. Patients whose tumors had high levels of this glycan on immune cells had worse survival outcomes. We think that this glycan controls the immune response and when expression levels are high, it prevents immune cell activation. To study how this glycan regulates the anti-tumor response, we propose to identify the immune cell subsets carrying this glycan and then study how this glycan effects their tumor killing functions. Our work will provide important details to help us understand how to trigger the anti-tumor immune response and may provide a new immune-checkpoint target for therapeutic development.