iFIT Seminar Series with Prof. Dr. Edward Graves
Biological and physical questions for combined radiotherapy and immunotherapy
Dr. Edward “Ted” Graves is an Associate Professor of Radiation Oncology and, by courtesy, Radiology at Stanford University. He directs the Imaging Radiobiology Laboratory, whose mission is to develop and apply novel molecular imaging strategies to understand tissue response to radiotherapy and to improve control of tumors with radiation. The response of biological tissues to radiotherapy has historically been interpreted in terms of the direct killing effect of radiation mediated by damage to cellular DNA. However, over the last half century the ability of radiation to induce a myriad of biological responses both within and beyond the irradiated field has been recognized. In particular, stimulating and inhibitory effects of radiotherapy on immune responses have been widely studied. The significance of these processes has been revisited with the rise of cancer immunotherapies designed to utilize a patient’s own immune system to identify and kill cancer cells. A number of studies have explored the use of radiation in combination with immunotherapy to enhance the immune stimulatory effects of this therapy, but results have been mixed. Clearly our knowledge of the precise spatial, temporal, and molecular determinants of immune response is incomplete. In this presentation I will describe progress in the study of immune responses following radiotherapy and how they can be leveraged through integration with immunotherapy. In particular I will present recent progress in combining radiotherapy with macrophage-mediated immunotherapies targeting “don’t eat me signals” that inhibit phagocytosis. I will emphasize questions that require understanding of not only the biological processes governing radiation and immune response but also of the physical dose distribution received by different tissues. This emerging area therefore requires close collaboration between radiation biologists and physicists in order to fully exploit its potential to improve cancer treatment in the clinic.