Immunotherapy and radiotherapy - a future partnership Focus on radiation induced lymphopenia (RIL) implications.

The hematological toxicity associated with radiotherapy is represented by neutropenia, anemia, thrombocytopenia, being associated with the increased risk of infection with opportunists, with fatigue and intolerance to effort, but also with the increased risk of bleeding. In the context of the preclinical and clinical results that mention the synergistic effect of the immunotherapy-radiotherapy association, radiation-induced lymphopenia (RIL) becomes an immunosuppression factor, a factor that would tip the fragile antitumor immunopotentiation-immunosuppression balance in favor of the immunosuppressive effect. Both the number of lymphocytes and the neutrophil/lymphocyte ratio (NLR) are prognostic and predictive biomarkers, providing information on the immune status of the host and on a possible response of the tumor to immunotherapy. Modern radiation techniques can increase the risk of lymphopenia by irradiating large volumes of tissue with low doses of radiation. In this context, a redefinition of the dose-volume constraints and the definition of bone marrow, lymphoid organs and lymph nodes not involved in tumors as organs at risk (OARs) is strictly necessary in the case of using irradiation through intensity-modulated radiation therapy (IMRT) techniques or volumetric modulated arc therapy (VMAT) for solid tumors that benefit from immune checkpoint inhibitor (ICI) therapy (Ref. 22). Text in PDF www.elis.sk Keywords: lymphopenia, immunotherapy, radiotherapy, toxicity, spleen, nodes irradiation.