Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, China.
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
Mol Cancer. 2023 Apr 13;22(1):70. doi: 10.1186/s12943-023-01772-4.
Immunotherapy has emerged to play a rapidly expanding role in the treatment of cancers. Currently, many clinical trials of therapeutic agents are on ongoing with majority of immune checkpoint inhibitors (ICIs) especially programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1, two main immune checkpoints, are expressed at high levels in thymic epithelial tumors (TETs) and could be predictors of the progression and immunotherapeutic efficacy of TETs. However, despite inspiring efficacy reported in clinical trials and clinical practice, significantly higher incidence of immune-related adverse events (irAEs) than other tumors bring challenges to the administration of ICIs in TETs. To develop safe and effective immunotherapeutic patterns in TETs, understanding the clinical properties of patients, the cellular and molecular mechanisms of immunotherapy and irAEs occurrence are crucial. In this review, the progress of both basic and clinical research on immune checkpoints in TETs, the evidence of therapeutic efficacy and irAEs based on PD-1 /PD-L1 inhibitors in TETs treatment are discussed. Additionally, we highlighted the possible mechanisms underlying irAEs, prevention and management strategies, the insufficiency of current research and some worthy research insights. High PD-1/PD-L1 expression in TETs provides a rationale for ICI use. Completed clinical trials have shown an encouraging efficacy of ICIs, despite the high rate of irAEs. A deeper mechanism understanding at molecular level how ICIs function in TETs and why irAEs occur will help maximize the immunotherapeutic efficacy while minimizing irAEs risks in TET treatment to improve patient prognosis.
免疫疗法在癌症治疗中发挥着迅速扩大的作用。目前，许多治疗药物的临床试验正在进行中，其中大多数免疫检查点抑制剂（ICI），尤其是程序性死亡受体 1（PD-1）及其配体 1（PD-L1）抑制剂。PD-1 和 PD-L1 是两个主要的免疫检查点，在胸腺瘤（TETs）中高表达，可能是 TETs 进展和免疫治疗疗效的预测因子。然而，尽管在临床试验和临床实践中报告了令人鼓舞的疗效，但与其他肿瘤相比，免疫相关不良事件（irAEs）的发生率明显更高，这给 TETs 中 ICI 的给药带来了挑战。为了在 TETs 中开发安全有效的免疫治疗模式，了解患者的临床特征、免疫治疗和 irAEs 发生的细胞和分子机制至关重要。在这篇综述中，讨论了 TETs 中免疫检查点的基础和临床研究进展、基于 PD-1/PD-L1 抑制剂在 TETs 治疗中的疗效和 irAEs 证据。此外，我们强调了 irAEs 潜在机制、预防和管理策略、当前研究的不足以及一些值得研究的见解。TETs 中高 PD-1/PD-L1 表达为 ICI 应用提供了依据。已完成的临床试验表明，ICI 具有令人鼓舞的疗效，尽管 irAEs 发生率较高。在分子水平上更深入地了解 ICI 在 TETs 中的作用机制以及 irAEs 发生的原因，将有助于在 TET 治疗中最大限度地提高免疫治疗疗效，同时最大限度地降低 irAEs 风险，以改善患者预后。
