Department of Thoracic Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Laboratory of Translational Medicine, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Mol Cancer. 2023 Jul 29;22(1):121. doi: 10.1186/s12943-023-01826-7.
Interleukin-2 (IL-2) and its receptor (IL-2R) are essential in orchestrating immune responses. Their function and expression in the tumor microenvironment make them attractive targets for immunotherapy, leading to the development of IL-2/IL-2R-targeted therapeutic strategies. However, the dynamic interplay between IL-2/IL-2R and various immune cells and their dual roles in promoting immune activation and tolerance presents a complex landscape for clinical exploitation. This review discusses the pivotal roles of IL-2 and IL-2R in tumorigenesis, shedding light on their potential as diagnostic and prognostic markers and their therapeutic manipulation in cancer. It underlines the necessity to balance the anti-tumor activity with regulatory T-cell expansion and evaluates strategies such as dose optimization and selective targeting for enhanced therapeutic effectiveness. The article explores recent advancements in the field, including developing genetically engineered IL-2 variants, combining IL-2/IL-2R-targeted therapies with other cancer treatments, and the potential benefits of a multidimensional approach integrating molecular profiling, immunological analyses, and clinical data. The review concludes that a deeper understanding of IL-2/IL-2R interactions within the tumor microenvironment is crucial for realizing the full potential of IL-2-based therapies, heralding the promise of improved outcomes for cancer patients.
白细胞介素-2（IL-2）及其受体（IL-2R）在协调免疫反应中起着至关重要的作用。它们在肿瘤微环境中的功能和表达使它们成为免疫治疗的有吸引力的靶点，导致 IL-2/IL-2R 靶向治疗策略的发展。然而，IL-2/IL-2R 与各种免疫细胞之间的动态相互作用及其在促进免疫激活和耐受方面的双重作用，为临床开发带来了复杂的局面。
本综述讨论了 IL-2 和 IL-2R 在肿瘤发生中的关键作用，阐明了它们作为诊断和预后标志物的潜力，以及它们在癌症中的治疗干预。强调需要平衡抗肿瘤活性与调节性 T 细胞的扩增，并评估各种策略，如优化剂量和选择性靶向，以提高治疗效果。
文章探讨了该领域的最新进展，包括开发基因工程化的 IL-2 变体，将 IL-2/IL-2R 靶向治疗与其他癌症治疗相结合，以及整合分子谱分析、免疫分析和临床数据的多维方法的潜在益处。综述结论认为，深入了解肿瘤微环境中 IL-2/IL-2R 的相互作用对于充分发挥基于 IL-2 的治疗潜力至关重要，为癌症患者带来更好的治疗效果提供了希望。
