免疫治疗在侵袭性胸腺瘤中的研究进展

Research Progress of Immunotherapy in Ag-gressive Thymomas

摘要: 侵袭性胸腺瘤具有不同的临床特征和预后。最具侵袭性且具有更大转移扩散趋势的亚型是胸腺癌。这些肿瘤因广泛的肿瘤扩散，手术切除往往达不到治愈目的，因此需要有效的非手术治疗。然而，尽管一些化疗方案已被证明有效，但除铂基化疗外的标准治疗方法尚不明确，近年来，免疫治疗在其他恶性肿瘤中表现出积极的临床疗效，使之有可能成为难治性TETs的治疗选择。胸腺肿瘤细胞上PD-L1的高表达和丰富的CD8+淋巴细胞，为靶向PD-1/PD-L1通路的免疫检查点抑制剂(ICIs)在胸腺上皮肿瘤中的治疗提供有力的依据，在现有的文献中表明，PD-L1的高表达是反应免疫治疗的预测因子。然而，与其他癌症患者相比，接受免疫检查点抑制剂治疗的TET患者更倾向于发生肌肉骨骼和神经肌肉等不良事件。目前，ICIs在TET中的疗效及标准治疗方案还有待肯定，需要更大规模的临床试验来确定ICIs的有效性和安全性。本文综述了TETs的生物学及其对免疫治疗耐受性的潜在影响和免疫检查点抑制剂的临床实验结果，以了解免疫治疗的潜在风险和益处。为了优化这些治疗难治性TETs的药物，目前迫切需要进一步的临床研究来评估免疫治疗药物的可用性，并描述它们对免疫治疗靶点的基本作用机制。目的是总结免疫治疗在治疗TETs中的临床研究进展。未来的研究应侧重于识别TETs患者的预测性生物标志物，并应实施多中心合作和针对罕见肿瘤类型的适当临床试验，使免疫治疗成为晚期胸腺肿瘤治疗的可行替代方案。

Abstract: Invasive thymoma has different clinical characteristics and prognosis. The most invasive subtype with a greater tendency for metastasis and spread is thymic cancer. Due to the widespread spread of these tumors, surgical resection often fails to achieve the goal of cure, thus requiring effective non-surgical treatment. However, although some chemotherapy regimens have been proven effec-tive, the standard treatment methods other than platinum based chemotherapy are not yet clear. In recent years, immunotherapy has shown positive clinical efficacy in other malignant tumors, making it a potential treatment option for refractory TETs. The high expression of PD-L1 and abun-dant CD8+lymphocytes on thymic tumor cells provide strong evidence for the treatment of thymic epithelial tumors with immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway. Ex-isting literature suggests that high expression of PD-L1 is a predictive factor for reactive immuno-therapy. However, compared to other cancer patients, TET patients treated with immune check-point inhibitors are more prone to adverse events such as musculoskeletal and neuromuscular events. At present, the efficacy and standard treatment plan of ICIs in TET still need to be confirmed, and larger clinical trials are needed to determine the effectiveness and safety of ICIs. This article reviews the biology of TETs and their potential impact on immunotherapy tolerance, as well as clin-ical experimental results of immune checkpoint inhibitors, in order to understand the potential risks and benefits of immunotherapy. In order to optimize these drugs for treating refractory TETs, further clinical research is urgently needed to evaluate the availability of immunotherapy drugs and describe their basic mechanisms of action on immunotherapy targets. The purpose is to sum-marize the clinical research progress of immunotherapy in the treatment of TETs. Future research should focus on identifying predictive biomarkers for patients with TETs, and implement multicen-ter collaboration and appropriate clinical trials targeting rare tumor types to make immunotherapy a feasible alternative to the treatment of advanced thymic tumors.