Jiao Rubin, Dadachova Ekaterina
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.
Immunotargets Ther. 2025 Jul 15;14:755-759. doi: 10.2147/ITT.S485643. eCollection 2025.
Combining external beam radiation therapy (EBRT) with immunotherapy showed promise pre-clinically by inducing immunogenic cell death (ICD) thus releasing damage-associated molecular patterns (DAMPs) and cytokines to activate the immune system. Clinical results, however, have often been disappointing. Radioligand therapy (RL), which uses targeted radionuclides to deliver cytotoxic radiation, offers advantages over EBRT by treating multiple tumors simultaneously. Combining RL with immunotherapy faces challenges, as prolonged radiation exposure can damage immune cells, and the "cross-fire" and "bystander" effects may harm incoming effector cells. Current RL therapies require multiple doses, further complicating immune cell viability. To optimize RL-immunotherapy combinations, timing is critical. Administering immunotherapy weeks after RL therapy may reduce radiation-induced immune cell damage. Additionally, selecting radionuclides with shorter half-lives could minimize immune cell toxicity while maintaining tumor-killing efficacy. Future RL therapies should prioritize radionuclides with optimal emission profiles and half-lives to enhance synergy with immunotherapy and improve clinical outcomes.
将外照射放疗（EBRT）与免疫疗法相结合在临床前研究中显示出前景，通过诱导免疫原性细胞死亡（ICD）从而释放损伤相关分子模式（DAMPs）和细胞因子来激活免疫系统。然而，临床结果往往令人失望。放射性配体疗法（RL）利用靶向放射性核素传递细胞毒性辐射，通过同时治疗多个肿瘤比EBRT具有优势。将RL与免疫疗法相结合面临挑战，因为长时间的辐射暴露会损害免疫细胞，并且“交叉火力”和“旁观者”效应可能会伤害进入的效应细胞。目前的RL疗法需要多次给药，这进一步使免疫细胞的生存能力复杂化。为了优化RL与免疫疗法的组合，时机至关重要。在RL治疗数周后给予免疫疗法可能会减少辐射诱导的免疫细胞损伤。此外，选择半衰期较短的放射性核素可以在保持肿瘤杀伤疗效的同时将免疫细胞毒性降至最低。未来的RL疗法应优先选择具有最佳发射谱和半衰期的放射性核素，以增强与免疫疗法的协同作用并改善临床结果。
