Understanding the impact of radiation-induced lymphopenia: Preclinical and clinical research perspectives

Immunotherapy has revolutionized the field of cancer treatment, changing the standard of care to the use of immune checkpoint inhibitors. Radiotherapy can boost anti-tumour immune responses by changing the tumour microenvironment, but it also can cause radiotherapy-induced lymphopenia (RIL), a decrease in circulating lymphocyte counts. RIL has been associated with lower survival in patients undergoing radiotherapy, and new studies have suggested that it can also affect immunotherapy outcome. To study RIL's effects and to explore mitigation treatment strategies, preclinical models closely mimicking the clinical situation are needed. State-of-the-art image-guided small animal irradiators now offer the possibility to target specific organs in small animals to induce RIL, aiding research on its molecular mechanisms and prevention. This review covers the relationship between radiotherapy and RIL, its impact on patient survival, and future directions to generate models to investigate and prevent RIL.