垂体腺瘤中 PD-L1 和 CD8 淋巴细胞的表达谱提示免疫治疗。
The expression profile of PD-L1 and CD8 lymphocyte in pituitary adenomas indicating for immunotherapy.
机构信息
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Department of Pathology, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
出版信息
J Neurooncol. 2018 Aug;139(1):89-95. doi: 10.1007/s11060-018-2844-2. Epub 2018 Apr 21.
BACKGROUND
Pituitary adenomas (PAs) are the second most common brain tumors, and mostly are benign tumors. However, there exists subtypes of PAs refractory to common treatments, and need novel therapy. Programmed death 1 (PD-1) blockade has shown durable objective response in a variety of malignancies, and the key predictive markers for this immunotherapy were PD-L1 and CD8 tumor-infiltrating lymphocyte (TILs) expression. To evaluate the potential immunotherapy for PAs, we investigated the expression of these two immune markers in PAs.
METHODS
Immunohistochemistry (IHC) was performed to detect the expression of PD-L1 and CD8 TILs in PAs. The ratio of positive expression of PD-L1 and CD8 TILs was compared with chi-squared tests among different subtypes of PAs. The association between their expression profile and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate.
RESULTS
One hundred and ninety one patients with PAs were retrospectively involved in this study, consisting of 106 non-functioning PAs (NF-PAs, 55.5%), 40 PRL-secreting PAs (PRL-PAs, 20.9%), 31 GH-secreting PAs (GH-PAs, 16.2%), 9 ACTH-secreting PAs (ACTH-PAs, 4.7%) and 5 plurihormonal adenomas (2.6%) respectively. 36.6% of them were PD-L1 positive and 86.9% were CD8 TILs positive. The positive PD-L1 immunostaining presented more frequently in functioning PAs (58.8%), compared with that (34.3%) in nonfunctioning group (p = 0.000). Moreover, the rates of PD-L1 expression were more associated with increased blood levels of PRL, GH, ACTH and cortisol. Contrastly, positive CD8 TILs immunostaining was only correlated with elevated blood level of GH. For the analysis of immune markers with pathological results, PD-L1 expression was associated with PRL and GH immunostaining and higher Ki-67 index. But CD8 TILs was only correlated with PRL immunostaining.
CONCLUSION
Our results showed that PD-L1 was frequently expressed in functioning PAs with association of aggressive behaviors in PAs. The immunotherapy could be a promising treatment option of PAs.
背景
垂体腺瘤（PA）是第二大常见脑肿瘤，多为良性肿瘤。然而，存在对常见治疗方法耐药的 PA 亚型，需要新的治疗方法。程序性死亡 1（PD-1）阻断已在多种恶性肿瘤中显示出持久的客观反应，这种免疫疗法的关键预测标志物是 PD-L1 和 CD8 肿瘤浸润淋巴细胞（TILs）的表达。为了评估 PA 的潜在免疫治疗，我们研究了这些两种免疫标志物在 PA 中的表达。
方法
通过免疫组织化学（IHC）检测 PA 中 PD-L1 和 CD8 TIL 的表达。通过卡方检验比较不同 PA 亚型之间 PD-L1 和 CD8 TIL 阳性表达的比例。使用卡方检验或Fisher 确切概率检验（当适用时）分析其表达谱与临床参数之间的关系。
结果
本研究回顾性纳入 191 例 PA 患者，其中包括 106 例无功能 PA（NF-PA，55.5%）、40 例催乳素分泌性 PA（PRL-PA，20.9%）、31 例生长激素分泌性 PA（GH-PA，16.2%）、9 例促肾上腺皮质激素分泌性 PA（ACTH-PA，4.7%）和 5 例多激素腺瘤（2.6%）。它们中有 36.6%的 PD-L1 阳性，86.9%的 CD8 TIL 阳性。功能性 PA 的阳性 PD-L1 免疫染色更常见（58.8%），而非功能性组（34.3%）（p=0.000）。此外，PD-L1 表达率与 PRL、GH、ACTH 和皮质醇的血液水平升高更相关。相反，阳性 CD8 TIL 免疫染色仅与 GH 血液水平升高相关。对于免疫标志物与病理结果的分析，PD-L1 表达与 PRL 和 GH 免疫染色和较高的 Ki-67 指数相关。但是 CD8 TIL 仅与 PRL 免疫染色相关。
结论
我们的结果表明，PD-L1 在具有侵袭性行为的功能性 PA 中频繁表达。免疫疗法可能是 PA 的一种有前途的治疗选择。
Zotero 插件