Recent advances in immuno-oncology have led to spectacular responses to immunotherapy (IO) (Rao et al., 2019). However, the majority of patients do not respond to these treatments. Clinicians, supported by recent research, now seem to be turning to therapeutic strategies combining not only IO and targeted therapies, but also conventional treatments such as radiotherapy (RT) and chemotherapy (CT) (Meric-Bernstam et al., 2021). Chemoradiation (CRT) represents a standard curative treatment for several locally advanced cancers including rectal, lung, and head and neck cancers (Rallis et al., 2021). According to the American Cancer Society, 35% in advanced stage of non-small cell lung cancers (stages III/IV) and 6% in localized stage (stages I/II) are treated with CRT in the United States.

RT and CT immune effects as monotherapies are widely described which is not the case for CRT (Zitvogel et al., 2013). Understanding CRT effects could help to overcome the resistance mechanisms often observed with IO and potentially reversible by combining CRT with other therapies (Vasan et al., 2019). In this review, we will describe the immunological effects induced by these combinations. Overall, CRT effects depend on the CT used the modalities of RT (Boustani et al., 2021a), and also the cancer-treated histology. Throughout this review, it should be kept in mind that the combined result of these two therapies is not only the addition or synergy of effect. Indeed, we propose a more complex model associating at the same time individual effects coming from each monotherapy but also effects only found during the combination (Fig. 1).