Grant: Project Grant

With few exceptions, surgery remains the most effective treatment for patients with solid tumors. However, the trauma of undergoing surgery invariably leads to a weakened immune system which contributes to the likelihood of the tumour reappearing and spreading throughout the patient's body. Natural killer (NK) cells, as their name suggests, are proficient at surveying the body and destroying any cancer cells that appear before they can develop into solid tumours. Although the importance of NK cells in controlling tumour growth is well recognized, my research has shown that surgery dramatically impairs their ability to recognize and respond to tumour cells. Unfortunately, there is no current strategy for addressing the suppression in NK cell activity which occurs following surgery and new approaches targeting this critical stage may hold the potential for improving patient outcomes. We have recently shown that following surgery a large number highly immune suppressive cells are released from the bone marrow and that strategies that prevent their interaction with NK cells can have beneficial effects in animal models. Therefore, we believe that targeting these myeloid derived suppressor cells (MDSCs) in patients may provide an effective approach for reversing the immune suppressive effects of surgery. To accomplish this goal we have attempted to identify ways of targeting the MDSC population that arises following surgery. These efforts have revealed a distinct identifier present only on MDSCs which we propose can be used to deliver a drug to inhibit their suppressive activity ultimately restoring normal NK cell activity. The current proposal seeks to answer whether this strategy would be safe and effective prior to use in cancer surgery patients. Considering that over 65,000 Canadians undergo tumour removal surgery each year, we believe this research has the potential to benefit a significant number of Canadians and cancer patients throughout the world.