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胸腺瘤与免疫检查点抑制剂

Thymic tumors and immune checkpoint inhibitors.

作者信息

Yokoyama Shintaro, Miyoshi Hiroaki

机构信息

Department of Surgery, Kurume University School of Medicine, Kurume, Japan.

Department of Pathology, Kurume University School of Medicine, Kurume, Japan.

出版信息

J Thorac Dis. 2018 May;10(Suppl 13):S1509-S1515. doi: 10.21037/jtd.2017.10.157.

Abstract

Thymoma and thymic carcinoma, known as the most common features of thymic epithelial tumors (TETs), are thoracic malignancies displaying varied clinical features and prognosis. These neoplasms being frequently ineligible for surgical complete resection as a curative treatment because of extensive tumor spread, effectual nonsurgical treatments are needed; however, an optimal chemotherapeutic regimen has not been identified, although some regimens have been shown to be active. Immunotherapy is effective for other malignancies and may be promising as a therapeutic alternative for refractory TETs. Thus far, several studies have determined the expression of programmed death ligand 1 (PD-L1) and programmed death 1 (PD-1) in TETs, including its clinicopathological and prognostic significance. The results have been conflicting due to the different immunohistochemical antibodies employed and distinct cutoff values. However, many authors identified abundant PD-L1 expression in TETs, which is considered as an important predictive factor for therapeutic effect of PD-1 inhibitors in other malignant tumors. In some clinical trials, an acceptable clinical efficacy of PD-1 inhibitor for TETs has been reported as expected; however, concerns regarding immunological adverse events have been raised. To optimize these therapeutic agents for refractory TETs, additional studies which evaluate clinical availabilities of immunotherapeutic drugs and characterize their basic mechanisms of action against immunotherapeutic targets are both urgently required.

摘要

胸腺瘤和胸腺癌是胸腺上皮肿瘤(TETs)最常见的特征,属于胸部恶性肿瘤,具有多样的临床特征和预后情况。由于肿瘤广泛扩散,这些肿瘤常常无法通过手术完全切除来进行根治性治疗,因此需要有效的非手术治疗方法;然而,尽管一些化疗方案已显示出活性,但尚未确定最佳的化疗方案。免疫疗法对其他恶性肿瘤有效,作为难治性TETs的治疗选择可能很有前景。到目前为止,多项研究已确定程序性死亡配体1(PD-L1)和程序性死亡1(PD-1)在TETs中的表达情况,包括其临床病理意义和预后意义。由于使用的免疫组化抗体不同以及临界值不同,结果一直存在争议。然而,许多作者发现TETs中存在大量PD-L1表达,这被认为是PD-1抑制剂对其他恶性肿瘤治疗效果的重要预测因素。在一些临床试验中,已报道PD-1抑制剂对TETs具有预期的可接受临床疗效;然而,人们也对免疫不良反应提出了担忧。为了为难治性TETs优化这些治疗药物,迫切需要开展更多研究,以评估免疫治疗药物的临床可用性,并阐明其针对免疫治疗靶点的基本作用机制。

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