PD-L1、转化生长因子-β表达和肿瘤浸润 CD8 T 细胞对晚期胸腺癌患者临床结局的影响。
Impact of PD-L1, transforming growth factor-β expression and tumor-infiltrating CD8 T cells on clinical outcome of patients with advanced thymic epithelial tumors.
机构信息
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Interventional Oncology, Dong Ying People's Hospital, Dongying, China.
出版信息
Thorac Cancer. 2018 Nov;9(11):1341-1353. doi: 10.1111/1759-7714.12826. Epub 2018 Aug 31.
BACKGROUND
Advanced thymic epithelial tumors (TETs) are indolent and poorly responsive to chemotherapy. PD-1/PD-L1 inhibitors have shown remarkable clinical benefit in several cancers; however, many immunomodulatory molecules have been identified that affect the immune response. This study examined the progonostic roles of PD-L1, transforming growth factor-β (TGF-β), and CD8 tumor-infiltrating lymphocytes (CD8 TILs) in patients with TETs.
METHODS
Retrospective analysis was performed on the data of 20 patients with stage IV thymic carcinoma and 13 with stage III/IV invasive thymoma. Tissue biopsies were obtained before first-line chemotherapy was administered. Protein levels were assessed by immunohistochemistry. Objective response rate, overall survival (OS), and progression-free survival (PFS) were analyzed.
RESULTS
Patients with advanced thymic carcinoma exhibited higher levels of PD-L1 and TGF-β than patients with advanced invasive thymic carcinoma (PD-L1: 65.0% vs. 46.2%, P = 0.472; TGF-β: 65.0% vs. 15.4%, P = 0.011). Five advanced thymic carcinoma patients with low levels of PD-L1 and TGF-β exhibited high levels of CD8 staining. The median OS was 29.5 months patients with high TGF-β expression versus 62.9 in patients with low TGF-β (P = 0.052). In patients with advanced thymic carcinoma, the median PFS in the high PD-L1 expression group was 13.3 months versus 23.5 (P = 0.043) in the low PD-L1, and the median OS was 50.7 months in the high CD8 expression versus 15.1 in the CD8 low group (P = 0.154).
CONCLUSIONS
Our results showed the prognostic roles of PD-L1, TGF-β, and CD8 TILs in patients with advanced TETs, and the potential for development of anti-PD-1/PD-L1 therapies.
背景
高级胸腺上皮肿瘤（TET）生长缓慢，对化疗反应不佳。PD-1/PD-L1 抑制剂在几种癌症中显示出显著的临床获益，但已发现许多免疫调节分子会影响免疫反应。本研究探讨了 PD-L1、转化生长因子-β（TGF-β）和 CD8 肿瘤浸润淋巴细胞（CD8 TIL）在 TET 患者中的预后作用。
方法
对 20 例 IV 期胸腺癌和 13 例 III/IV 期侵袭性胸腺瘤患者的数据进行回顾性分析。在一线化疗前获取组织活检。通过免疫组织化学评估蛋白水平。分析客观缓解率、总生存期（OS）和无进展生存期（PFS）。
结果
晚期胸腺癌患者的 PD-L1 和 TGF-β 水平高于晚期侵袭性胸腺癌患者（PD-L1：65.0%比 46.2%，P=0.472；TGF-β：65.0%比 15.4%，P=0.011）。5 例 PD-L1 和 TGF-β 水平较低的晚期胸腺癌患者 CD8 染色水平较高。高 TGF-β 表达患者的中位 OS 为 29.5 个月，低 TGF-β 表达患者为 62.9 个月（P=0.052）。在晚期胸腺癌患者中，高 PD-L1 表达组的中位 PFS 为 13.3 个月，低 PD-L1 表达组为 23.5 个月（P=0.043），高 CD8 表达组的中位 OS 为 50.7 个月，低 CD8 表达组为 15.1 个月（P=0.154）。
结论
我们的研究结果表明，PD-L1、TGF-β 和 CD8 TILs 在晚期 TET 患者中具有预后作用，为开发抗 PD-1/PD-L1 治疗方法提供了依据。
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