The role of immunotherapy for management of advanced thymic epithelial tumors: a narrative review.
The role of immunotherapy for management of advanced thymic epithelial tumors: a narrative review.
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DOI：
10.21037/med-20-62
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发表时间：
2021-09-01
期刊：
影响因子：
--
通讯作者：
Zhao, Chen
中科院分区：
文献类型：
--
作者：
Rajan, Arun;Mullenix, Cristina;Zhao, Chen
免疫疗法作为现代癌症治疗支柱的出现改变了各种癌症的治疗格局。特别是针对程序性死亡 1 (PD-1) 或其配体 (PD-L1) 的免疫检查点抑制剂已发现广泛的临床应用，并导致持久的反应并提高晚期或转移性疾病患者的生存率。肿瘤细胞 PD-L1 表达和肿瘤突变负荷 (TMB) 是反应的生物标志物，我们正在努力识别可能预测这些药物获益的其他生物标志物。大多数患者对免疫治疗的耐受性良好，尽管一部分患者由于过度的免疫刺激而出现免疫介导的毒性。胸腺上皮肿瘤（TET）具有独特的生物学特性，可能导致自身免疫性副肿瘤疾病的发生，尤其是胸腺瘤患者。由于免疫自我耐受的缺陷，TET 患者使用免疫治疗会增加免疫介导的不良事件的风险，从而可能危及生命。反应和毒性生物标志物的开发对于 TET 的治疗尤其重要，因为确定可能从治疗中受益且发生严重免疫毒性的风险较低的患者非常重要。在患有自身免疫性疾病的患者和先前经历过免疫介导的毒性的患者中使用免疫疗法是目前活跃的研究领域。前瞻性临床试验正在评估各种风险缓解策略，包括胸腺癌患者的免疫检查点抑制剂试验。
The emergence of immunotherapy as a modern pillar of cancer treatment has changed the treatment landscape for various cancers. Immune checkpoint inhibitors directed at programed death-1 (PD-1) or its ligand (PD-L1), in particular, have found widespread clinical applications and have resulted in durable responses and an improvement in survival of patients with advanced or metastatic disease. Tumor cell PD-L1 expression and tumor mutation burden (TMB) are biomarkers of response and efforts are underway to identify other biomarkers that might predict benefit with these drugs. Most patients tolerate immunotherapy well, although a subset of patients develop immune-mediated toxicity due to excessive immune stimulation. Thymic epithelial tumors (TETs) have a unique biology which can predispose to development of autoimmune paraneoplastic disease, especially in patients with thymoma. Due to defects in immunological self-tolerance, the use of immunotherapy in TET patients is associated with an increased risk of immune-mediated adverse events, which can be potentially life-threatening. Development of biomarkers of response and toxicity is particularly important for the treatment of TETs since it is important to identify patients who might benefit from treatment and be at low risk for development of severe immune toxicity. The use of immunotherapy in patients with autoimmune disorders and those who have previously experienced immune-mediated toxicity is currently an area of active research. Various risk mitigation strategies are under evaluation in prospective clinical trials, including trials of immune checkpoint inhibitors in patients with thymic cancers.