Immunotherapy and radiotherapy


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Tim Illidge1
1Cancer Research UK Manchester Institute

Abstract

The translation of our increasing scientific knowledge about the key receptors involved in tumour immunoregulation, from proof of principle with anti-CTLA-4, to effective clinical anti-cancer therapeutics in a large range of cancers eg anti-PD1/ PD-L1 inhibitors has led to huge optimism that immunotherapy will play an increasingly important part in cancer therapy. In contrast radiation treatment (RT) has been established as highly effective cancer therapy for decades albeit the focus in radiobiology has largely been on the direct tumour cell kill. However emerging evidence suggests that RT also has important effects on the tumour microenvironment and can generate local anti-tumour immunity. The generation of systemic immunity and tumour responses outside of the radiation treatment area that leads to the so called “abscopal effect” are however extremely rare and this is thought to be secondary to tumour suppressive adaptive resistance.

The opportunity of combining RT and immunmodulatory agents however offer great potential to reverse the tumour induced resistance to improve outcomes further. In order to increase the number of responses in the majority of patients across many different tumour types, further investigation is required to fully understand the potential underlying mechanisms of resistance. In addition well-designed clinical trials with the appropriate translational research we also be required. In this presentation the interplay of RT with the tumour microenvironment and novel opportunities to overcome adaptive resistance will be discussed alongside clinical translation.