The implementation of novel
cancer immunotherapies in the form of
immune checkpoint blockers represents a major advancement in the treatment of
cancer, and has renewed enthusiasm for identifying new ways to induce antitumor immune responses in patients. Despite the proven efficacy of
neutralizing antibodies that target immune checkpoints in some refractory
cancers, many patients do not experience therapeutic benefit, possibly owing to a lack of antitumor immune recognition, or to the presence of dominant immunosuppressive mechanisms in the tumor microenvironment (TME). Recent developments in this field have revealed that local
radiotherapy (RT) can transform
tumors into in situ
vaccines, and may help to overcome some of the barriers to
tumor-specific immune rejection. RT has the potential to ignite
tumor immune recognition by generating immunogenic signals and releasing neoantigens, but the multiple immunosuppressive forces in the TME continue to represent important barriers to successful
tumor rejection. In this article, we review the radiation-induced changes in the stromal compartments of
tumors that could have an impact on
tumor immune attack. Since different RT regimens are known to mediate strikingly different effects on the multifarious elements of the
tumor stroma, special emphasis is given to different RT schedules, and the time
after treatment at which the effects are measured. A better understanding of TME remodeling following specific RT regimens and the window of opportunity offered by RT will enable optimization of the design of novel treatment combinations.