Radiotherapy: Changing the Game in Immunotherapy

Immune checkpoint inhibitors (ICI) are effective in cancer treatment. A preexisting immune response demonstrated by significant pretreatment tumor lymphocytic infiltration is a prerequisite for response. Within such infiltrated tumors, referred to as 'hot' tumors, ICI rescue the activity of antitumor T cells. By contrast, 'cold' tumors lack lymphocytic infiltration and are refractory to immunotherapy. Preclinical data show that radiotherapy sensitizes refractory tumors to ICI by recruiting antitumor T cells. Despite the growing number of clinical studies testing the ability of radiation to enhance immunotherapy, clinical evidence that it converts cold tumors into responsive ones remains elusive. Here, we review evidence that radiotherapy is not only an occasional enhancer of the effects of immunotherapy, but also a 'game changer', and propose a blueprint to test this.