Grant: CIHR Fellowship

Radiotherapy (RT), the use of ionizing radiation to treat tumors, represents a routine standard-of-care treatment option for Canadians diagnosed with cancer. Recent studies have illustrated that RT acts similar to a "vaccine"; promoting the recognition of cancer cells as dangerous targets for the immune system (i.e., anti-tumor T cell immunity). Such RT-induced anti-tumor immunity could eliminate cancer and prevent future relapse. Unfortunately, RT can also lead to suppressive effects, which both promote tumor progression and limit T cell immunity. Thus, it is crucial to understand the underlying mechanisms that dictate the "unwanted" suppressive effects and "desired" anti-tumor T cell immunity. This understanding would allow for the development of rationally designed combination therapies that enhance the success of RT. Dendritic cells (DCs) are pivotal immune cells in the regulation of both immune stimulation and suppression. For instance, tumors tend to favor the accumulation of suppressive DCs and other suppressive myeloid cells; whereas infections promote immunogenic DCs that have a unique ability to activate T cell immunity. Importantly, immunogenic DCs also reliably correlate with increased anti-tumor T cell immunity and cancer therapeutic efficacy. I hypothesize that modulation of immunogenic and suppressive DCs and other myeloid cells would significant impact the outcome RT. Thus, this research project aims to use cutting-edge technology, such as image-guided radiation technology and high parametric single-cell analysis (CyTOF), to mimic clinical RT practices and characterize the nature and function of DCs localized in the tumor, respectively. By exploiting such findings, I will implement rational combination therapies that promote immunogenic DCs or block the function of suppressive DCs. I am convinced that this project will uncover novel biological principles and positively impact the design of cancer treatment strategies.