Abstract
Immune checkpoint inhibitors are effective in cancer treatment. A pre-existing immune response demonstrated by significant pretreatment tumor lymphocytic infiltration is a pre-requisite for response. Within such infiltrated tumors, referred as "hot", immune checkpoint inhibitors rescue anti-tumor T cells activity. In contrast, "cold" tumors lack lymphocytic infiltration and are refractory to immunotherapy. Preclinical data show that radiotherapy sensitizes refractory tumors to immune checkpoint inhibitors by recruiting anti-tumor T cells. Despite the growing number of clinical studies testing radiation's ability 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 immunotherapy's effects but a "game changer", and propose a blueprint to test this.