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  • Review Article
  • Published:

Radiotherapy and immunotherapy: a beneficial liaison?

Key Points

  • Radiotherapy not only exerts direct cytotoxic effects on tumour cells, but also re-programmes the tumour microenvironment to exert a potent antitumour immune response

  • Tumour-cell proliferation and cell death due to T-cell cytotoxic killing coexist in irradiated tumours, resulting in stable disease that might provide a window of opportunity for immune-modulation

  • Radiotherapy enhances antitumour immunity, but also induces immunosuppressive responses

  • The combination of immunotherapy and radiotherapy presents a multimodal treatment approach that involves stimulating and suppressing various pathways

Abstract

Investigations into the interaction between radiotherapy and the host immune system have uncovered new mechanisms that can potentially be exploited to improve the efficacy of radiotherapy. Radiation promotes the release of danger signals and chemokines that recruit inflammatory cells into the tumour microenvironment, including antigen-presenting cells that activate cytotoxic T-cell function. By contrast, radiation can attract immunosuppressive cells into the tumour microenvironment. In rare circumstances, the antitumour effect of radiotherapy has been observed outside of the radiation field, known as the abscopal effect. This phenomenon is proposed to have an immune origin and indicates that local radiotherapy elicits systemic effects. Herein, we highlight data that provide new mechanistic explanations for the success or failure of radiotherapy, and postulate how the combination of immune-modulation and radiation could tip the balance of the host immune response to promote cure. We use the concept of radiation- induced tumour equilibrium (RITE) as a starting point to discuss the mechanistic influence of immune-checkpoint therapies on radiotherapy efficacy.

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Figure 1: Radiation-induced effects on tumour cells.
Figure 2: Host immune responses, not the radiosensitivity of cancer cells, correlate with efficacy of radiation therapy (RT).
Figure 3: Tumour-cell division coexists with apoptosis in stable tumours.

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Acknowledgements

The authors wish to thank Amy K. Huser at The University of Chicago for her invaluable literature-research, writing, and editing contributions to the historical passages of this Review, and Table 1 and Figure 1. The work of R.R.W is supported in part by NIH grant NCI-R21CA195075-01.

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R.R.W., H.L., and L.D. wrote the manuscript. All authors made substantial contributions to researching data for article, discussions of content, and review/editing of manuscript before submission.

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Correspondence to Ralph R. Weichselbaum.

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Weichselbaum, R., Liang, H., Deng, L. et al. Radiotherapy and immunotherapy: a beneficial liaison?. Nat Rev Clin Oncol 14, 365–379 (2017). https://doi.org/10.1038/nrclinonc.2016.211

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