1. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
2. Hubei Key Laboratory of Precision Radiation Oncology, Wuhan 430048, China.
3. University of Southern California, Department of Biochemistry and Molecular Medicine.
4. Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
5. Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, California 90095-1772, USA.
†These authors contributed equally to this work.
Interest surrounding the effect of irradiation on immune activation has exponentially grown within the last decade. This includes work regarding mechanisms of the abscopal effect and the success achieved by combination of radiotherapy and immunotherapy. It is hypothesized that irradiation triggers the immune system to eliminate tumors by inducing tumor cells immunogenic cell death (ICD) in tumor cells. Activation of the ICD pathways can be exploited as an in situ vaccine. In this review, we provide fundamental knowledge of various forms of ICD caused by irradiation, describe the relationship between various cell death pathways and the immune activation effect driven by irradiation, and focus on the therapeutic value of exploiting these cell death programs in the context of irradiation. Furthermore, we summarize the immunomodulatory effect of different cell death programs on combinative radiotherapy and immunotherapy. In brief, differences in cell death programs significantly impact the irradiation-induced immune activation effect. Evaluating the transition between them will provide clues to develop new strategies for radiotherapy and its combination with immunotherapy.
Keywords: Cell death programs, in situ vaccine, irradiation, immunotherapy