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Review

Radiotherapy–Immunotherapy Combination: How Will We Bridge the Gap Between Pre-Clinical Promise and Effective Clinical Delivery?

1
Division of Cancer Sciences, Faculty of Biology, School of Medical Sciences, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
2
Manchester Academic Health Science Centre, NIHR Biomedical Research Centre, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
*
Author to whom correspondence should be addressed.
Academic Editors: Rob P. Coppes and Marc A.G.G. Vooijs
Cancers 2021, 13(3), 457; https://doi.org/10.3390/cancers13030457
Received: 5 January 2021 / Revised: 18 January 2021 / Accepted: 21 January 2021 / Published: 26 January 2021
(This article belongs to the Special Issue Advances in Experimental Radiotherapy)
Radiotherapy is an important component of cancer treatment, given to around half of all cancer patients. Radiotherapy is known to be very effective at directly killing cancer but, until recently, the important effects that radiotherapy has on the surrounding immune cells were not widely appreciated. Over the last decade, immunotherapy approaches have made a major breakthrough in cancer treatment, and now play an important part of routine cancer care. Given that both radiotherapy and immunotherapy can stimulate anti-tumor immune response, it is logical to combine these approaches to try and improve anti-tumor immunity and cancer outcomes further. This review assesses the important clinical questions that need to be addressed to successfully combine radiotherapy and immunotherapy treatments by rethinking approaches to the delivery of radiotherapy, as well as the optimal type and scheduling of immunotherapy.
Radiotherapy (RT) is highly effective at directly killing tumor cells and plays an important part in cancer treatments being delivered to around 50% of all cancer patients. The additional immunomodulatory properties of RT have been investigated, and if exploited effectively, have the potential to further improve the efficacy of RT and cancer outcomes. The initial results of combining RT with immunomodulatory agents have generated promising data in pre-clinical studies, which has in turn led to a large number of RT and immunotherapy clinical trials. The overarching aim of these combinations is to enhance anti-tumor immune responses and improve responses rates and patient outcomes. In order to maximize this undoubted opportunity, there remain a number of important questions that need to be addressed, including: (i) the optimal RT dose and fractionation schedule; (ii) the optimal RT target volume; (iii) the optimal immuno-oncology (IO) agent(s) to partner with RT; (iv) the optimal site(s)/route(s) of administration of IO agents; and finally, the optimal RT schedule. In this review, we will summarize progress to date and identify current gaps in knowledge that need to be addressed in order to facilitate effective clinical translation of RT and IO agent combinations. View Full-Text
Keywords: radiotherapy; immunotherapy; immuno-oncology agents; radiotherapy dose; fractionation schedule; treatment field; tumor volume; administration site/route; administration sequencing radiotherapy; immunotherapy; immuno-oncology agents; radiotherapy dose; fractionation schedule; treatment field; tumor volume; administration site/route; administration sequencing
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MDPI and ACS Style

Romano, E.; Honeychurch, J.; Illidge, T.M. Radiotherapy–Immunotherapy Combination: How Will We Bridge the Gap Between Pre-Clinical Promise and Effective Clinical Delivery? Cancers 2021, 13, 457. https://doi.org/10.3390/cancers13030457

AMA Style

Romano E, Honeychurch J, Illidge TM. Radiotherapy–Immunotherapy Combination: How Will We Bridge the Gap Between Pre-Clinical Promise and Effective Clinical Delivery? Cancers. 2021; 13(3):457. https://doi.org/10.3390/cancers13030457

Chicago/Turabian Style

Romano, Erminia, Jamie Honeychurch, and Timothy M. Illidge 2021. "Radiotherapy–Immunotherapy Combination: How Will We Bridge the Gap Between Pre-Clinical Promise and Effective Clinical Delivery?" Cancers 13, no. 3: 457. https://doi.org/10.3390/cancers13030457

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