期刊
CANCER LETTERS
卷 502, 期 -, 页码 84-96出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.12.045
关键词
Radiotherapy; Immunotherapy; Abscopal effect; Immunogenic cell death; DAMPS; Hypofractionation
类别
资金
- CROSS Cancer Charity [RCN: 15364]
Immune checkpoint blockade has significantly changed the treatment of solid tumors, but many patients do not respond. Combining radiation therapy with immunotherapy may have synergistic effects by remodeling the tumor microenvironment, but careful control of dose and fractionation is essential for safety and efficacy. Ongoing efforts to combine radiation, immunotherapy, and DNA damage response inhibitors aim to achieve a beneficial balance between the immunogenic and tolerogenic effects of radiation on the immune microenvironment.
Immune checkpoint blockade (ICB) has revolutionised the treatment of solid tumours, yet most patients do not derive a clinical benefit. Resistance to ICB is often contingent on the tumour microenvironment (TME) and modulating aspects of this immunosuppressive milieu is a goal of combination treatment approaches. Radiation has been used for over a century in the management of cancer with more than half of all cancer patients receiving radiotherapy. Here, we outline the rationale behind combining radiotherapy with ICB, a potential synergy through mutually beneficial remodelling of the TME. We discuss the pleiotropic effects radiation has on the TME including immunogenic cell death, activation of cytosolic DNA sensors, remodelling the stroma and vasculature, and paradoxical infiltration of both anti-tumour and suppressive immune cell populations. These events depend on the radiation dose and fractionation and optimising these parameters will be key to develop safe and effective combination regimens. Finally, we highlight ongoing efforts that combine radiation, immunotherapy and inhibitors of DNA damage response, which can help achieve a favourable equilibrium between the immunogenic and tolerogenic effects of radiation on the immune microenvironment.
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