Abstract
Radiotherapy has been used for more than a hundred years to cure or locally control tumors. Regression of tumors outside of the irradiated field was occasionally observed and is known as the abscopal effect. However, the occurrence of systemic anti-tumor effects was deemed too rare and unpredictable to be a therapeutic goal. Recent studies suggest that immunotherapy and radiation in combination may enhance the abscopal response. Increasing numbers of cases are being reported since the routine implementation of immune checkpoint inhibitors, showing that combined radiotherapy with immunotherapy has a synergistic effect on both local and distant (i.e., unirradiated) tumors. In this review, we summarize pre-clinical and clinical reports, with a specific focus on the mechanisms behind the immunostimulatory effects of radiation and how this is enhanced by immunotherapy.
Highlights
Photons can be defined by their wavelength, frequency, or energy, with ionizing radiation consisting of photons with at least 10 electron-volts of energy
This study provides robust pre-clinical evidence for the importance of optimizing the timing of immunotherapeutic administration when designing clinical trials examining combination radiation therapy (RT) and immunotherapy
The largest prospective, randomized study assessing immune checkpoint inhibitors (ICI) addition to RT in patients was the PACIFIC trial (NCT02125461), showing an overall survival improvement for patients with locally advanced non-small-cell lung cancer (NSCLC) treated with adjuvant durvalumab after definitive intent fractionated chemoradiation (HR 0.68; 99.73% CI 0.47–0.997; p = 0.0025) [35]
Summary
Photons can be defined by their wavelength, frequency, or energy, with ionizing radiation consisting of photons with at least 10 electron-volts (eV) of energy. The use of T cell immune checkpoint inhibitors (ICI) to overcome cancer-mediated T cell inhibition including anti-PD-1, anti-PD-L1 and anti-CTLA-4 monoclonal antibodies has shown particular promise in patients with metastatic cancer [31,32,33,34], with encouraging results in animal models and clinical trials. New prospective studies and cases in humans have been reported, helping to clarify optimal patient selection [38,39], sequencing [40], targets [40,41], and possible limitations [42,43,44] for RT with ICI Despite this progress, much work is still needed given the diversity of tumors, presentations, and immune mechanisms involved
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