胸腺恶性肿瘤的副肿瘤性和治疗相关免疫并发症

Abstract

The thymus is a key organ involved in establishing central immune tolerance. Thymic epithelial tumors (TETs) include thymomas and thymic carcinomas. Thymomas, which are histologically distinct from thymic carcinomas, lead to dysregulated thymopoiesis via decreased thymic epithelial expression of AIRE and MHC Class II, as well as via alterations in thymic architecture, thereby resulting in autoimmune complications that manifest as paraneoplastic disorders (PNDs). 

胸腺是参与建立中枢免疫耐受的关键器官。胸腺上皮性肿瘤（TETs）包括胸腺瘤和胸腺癌。胸腺瘤在组织学上不同于胸腺癌，通过降低的AIRE和MHC II类的胸腺上皮表达以及胸腺结构的改变导致胸腺生成失调，从而导致表现为副肿瘤性疾病（PNDs）的自身免疫并发症。

Although progress has been made in elucidating the mechanisms underlying thymoma-associated PNDs, there remains a great need to further define the underlying mechanisms and to identify additional immune biomarkers, such as novel antibodies (in "seronegative" cases) to facilitate diagnosis and monitoring of patients. 

虽然在阐明胸腺瘤相关PNDs的潜在机制方面已经取得了进展，但仍然非常必要进一步确定潜在的机制并识别其他免疫生物学标记物，例如新型抗体（在“血清阴性”病例中）以促进诊断和监测患者。

In addition, a better understanding of the pathogenesis of PNDs could lead to improved treatment strategies for both thymomas and their immune complications. In advanced, refractory cases of TETs (both thymoma and thymic carcinoma), additional therapeutic approaches are needed. 

此外，更好地了解PNDs的发病机制可以改善胸腺瘤及其免疫并发症的治疗策略。在晚期难治性TET病例（包括胸腺瘤和胸腺癌），需要其他治疗方法。

Immune checkpoint inhibitors have revolutionized the treatment of several malignancies and hold promise in the treatment of TETs; however, the risks for immune-related adverse events (especially for inducing PNDs as well as in the setting of pre-existing PNDs) underscore the need to optimize patient selection and improve clinical management before there can be widespread acceptance of checkpoint inhibitor therapy in patients with TETs.