Modulation of CD8⁺ T Cell Responses by Radiotherapy-Current Evidence and Rationale for Combination with Immune Checkpoint Inhibitors

Radiotherapy for cancer has been known to affect the responses of immune cells, especially those of CD8⁺ T cells that play a pivotal role in anti-tumor immunity. Clinical success of immune checkpoint inhibitors led to an increasing interest in the ability of radiation to modulate CD8⁺ T cell responses. Recent studies that carefully analyzed CD8⁺ T cell responses following radiotherapy suggest the beneficial roles of radiotherapy on anti-tumor immunity. In addition, numerous clinical trials to evaluate the efficacy of combining radiotherapy with immune checkpoint inhibitors are currently undergoing. In this review, we summarize the current status of knowledge regarding the changes in CD8⁺ T cells following radiotherapy from various preclinical and clinical studies. Furthermore, key biological mechanisms that underlie such modulation, including both direct and indirect effects, are described. Lastly, we discuss the current evidence and essential considerations for harnessing radiotherapy as a combination partner for immune checkpoint inhibitors.