Immunotherapy of thymic epithelial tumors: molecular understandings and clinical perspectives.
Immunotherapy of thymic epithelial tumors: molecular understandings and clinical perspectives.
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DOI：
10.1186/s12943-023-01772-4
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发表时间：
2023-04-13
期刊：
影响因子：
37.3
通讯作者：
Ding, Jian-Yong
中科院分区：
文献类型：
--
作者：
Ao, Yong-Qiang;Gao, Jian;Wang, Shuai;Jiang, Jia-Hao;Deng, Jie;Wang, Hai-Kun;Xu, Bei;Ding, Jian-Yong
关键词：
免疫疗法在癌症治疗中发挥着迅速扩大的作用。目前，大多数免疫检查点抑制剂（ICI），特别是程序性死亡受体1（PD-1）及其配体1（PD-L1）抑制剂正在进行许多治疗药物的临床试验。PD-1和PD-L1是两个主要的免疫检查点，在胸腺上皮肿瘤（TCLT）中以高水平表达，并且可以预测TCLT的进展和免疫功效。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（irAE）的发生率显著较高，这给TBI的ICI给药带来了挑战。为了开发安全有效的免疫治疗模式，了解患者的临床特征，免疫治疗的细胞和分子机制以及irAE的发生至关重要。本文综述了近年来关于免疫检查点的基础和临床研究进展，以及PD-1 /PD-L1抑制剂在TGFAP治疗中的疗效证据和irAE。此外，我们强调了irAE的可能机制，预防和管理策略，目前研究的不足和一些值得研究的见解。Tcells中PD-1/PD-L1的高表达为ICI的使用提供了依据。已完成的临床试验显示，尽管irAE的发生率很高，但ICI的疗效令人鼓舞。从分子水平深入了解ICI在TET中的作用机制以及irAE发生的原因将有助于最大限度地提高免疫疗效，同时最大限度地降低泰特治疗中的irAE风险，以改善患者预后。
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.
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影响因子：
--
作者：
Arasanz H;Gato-Cañas M;Zuazo M;Ibañez-Vea M;Breckpot K;Kochan G;Escors D
通讯作者：
Escors D
DOI：
10.1084/jem.20131219
发表时间：
2013-10-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bouchlaka MN;Sckisel GD;Chen M;Mirsoian A;Zamora AE;Maverakis E;Wilkins DE;Alderson KL;Hsiao HH;Weiss JM;Monjazeb AM;Hesdorffer C;Ferrucci L;Longo DL;Blazar BR;Wiltrout RH;Redelman D;Taub DD;Murphy WJ
通讯作者：
Murphy WJ
影响因子：
2.3
作者：
Conlon, Kevin C.;Miljkovic, Milos D.;Waldmann, Thomas A.
通讯作者：
Waldmann, Thomas A.
影响因子：
10.9
作者：
Abou Alaiwi, Sarah;Xie, Wanling;Harshman, Lauren C.
通讯作者：
Harshman, Lauren C.
影响因子：
3.7
作者：
Arbour KC;Naidoo J;Steele KE;Ni A;Moreira AL;Rekhtman N;Robbins PB;Karakunnel J;Rimner A;Huang J;Riely GJ;Hellmann MD
通讯作者：
Hellmann MD