Radiation, Immunotherapy, and the Abscopal Effect: A Critical Review on Timing, Dose, and Fractionation.
- 1Department of Radiation Oncology, Emory University, United States
- 2Department of Microbiology and Immunology, Emory University, United States
- 3Department of Radiation Oncology, Henry Ford Health System, United States
- 4Erlanger UT Radiation Oncology, United States
- 5Mitchell Cancer Institute, Radiation Oncology, University of South Alabama, United States
- 6Georgia Cancer Center, United States
The combination of radiation and immunotherapy is currently an exciting avenue of pre-clinical and clinical investigation. The synergy between these two treatment modalities has the potential to expand the role of radiation from a purely local therapy, to a role in advanced and metastatic disease. Tumor regression outside of the irradiated field, known as the abscopal effect, is a recognized phenomenon mediated by lymphocytes and enhanced by checkpoint blockade. In this review, we summarize the known mechanistic data behind radiation’s immunostimulation, and how this is enhanced by immunotherapy. We also provide pre-clinical data supporting specific radiation timing and optimal dose/fractionation for induction of a robust anti-tumor immune response with or without checkpoint blockade. Importantly, these data are placed in a larger context of understanding T-cell exhaustion and the impact of immunotherapy on this phenotype. We also include relevant pre-clinical studies done in non-tumor systems. We discuss the published clinical trials and briefly summarize salient case reports evaluating the abscopal effect. Much of the data discussed here remains at the preliminary stage, and a number of interesting avenues of research remain under investigation
Keywords: Radiation, Immunotherapy, checkpoint blockade, PD-1, PD-L1, abscopal effect
Received: 27 Oct 2018;
Accepted: 29 Nov 2018.
Edited by:Udo S. Gaipl, Universitätsklinikum Erlangen, Germany
Reviewed by:Daniel Olive, Faculté de Médecine, Aix Marseille Université, France
Rodabe N. Amaria, University of Texas MD Anderson Cancer Center, United States
Copyright: © 2018 Buchwald, Wynne, Nasti, Zhu, Mourad, Yan, Gupta, Khlief and Khan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Mohammad K. Khan, Department of Radiation Oncology, Emory University, Atlanta, United States, email@example.com