Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Front Immunol. 2022 Oct 3;13:951817. doi: 10.3389/fimmu.2022.951817. eCollection 2022.
Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is an Epstein-Barr virus (EBV)-related, rare subtype of non-small-cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) show durable responses in advanced NSCLC. However, their effects and predictive biomarkers in PLELC remain poorly understood. We retrospectively analyzed the data of 48 metastatic PLELC patients treated with ICI. Pretreated paraffin-embedded specimens (n = 19) were stained for PD-1, PD-L1, LAG3, TIM3, CD3, CD4, CD8, CD68, FOXP3, and cytokeratin (CK) by multiple immunohistochemistry (mIHC). Next-generation sequencing was performed for 33 PLELC samples. Among patients treated with ICI monotherapy (n = 30), the objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and overall survival (mOS) were 13.3%, 80.0%, 7.7 months, and 24.9 months, respectively. Patients with PD-L1 ≥1% showed a longer PFS (8.4 . 2.1 months, = 0.015) relative to those with PD-L1 <1%. Among patients treated with ICI combination therapy (n = 18), ORR, DCR, mPFS, and mOS were 27.8%, 100.0%, 10.1 months, and 19.7 months, respectively. Patients with PD-L1 ≥1% showed a significantly superior OS than those with PD-L1 <1% (NA versus 11.7 months, = 0.001). Among the 19 mIHC patients, those with high PD-1/PD-L1 and LAG3 expression showed a longer PFS (19.0 . 3.9 months, = 0.003). ICI also showed promising efficacy for treating metastatic PLELC. PD-L1 may be both predictive of ICI treatment efficacy and prognostic for survival in PLELC. PD-1/PD-L1 combined with LAG3 may serve as a predictor of ICI treatment effectiveness in PLELC. Larger and prospective trials are warranted to validate both ICI activity and predictive biomarkers in PLELC. This study was partly presented as a poster at the IASLC 20th World Conference on Lung Cancer 2019, 7-10 September 2019, Barcelona, Spain.
原发性肺淋巴上皮瘤样癌（PLELC）是一种与 EBV 相关的非小细胞肺癌（NSCLC）的罕见亚型。免疫检查点抑制剂（ICI）在晚期 NSCLC 中显示出持久的反应。然而，它们在 PLELC 中的作用和预测生物标志物仍知之甚少。我们回顾性分析了 48 例接受 ICI 治疗的转移性 PLELC 患者的数据。对预处理的石蜡包埋标本（n = 19）进行 PD-1、PD-L1、LAG3、TIM3、CD3、CD4、CD8、CD68、FOXP3 和细胞角蛋白（CK）的多重免疫组化（mIHC）染色。对 33 例 PLELC 样本进行了下一代测序。在接受 ICI 单药治疗的患者（n = 30）中，客观缓解率（ORR）、疾病控制率（DCR）、中位无进展生存期（mPFS）和总生存期（mOS）分别为 13.3%、80.0%、7.7 个月和 24.9 个月。PD-L1≥1%的患者 PFS 较长（8.4. 2.1 个月， = 0.015），而 PD-L1<1%的患者 PFS 较短。在接受 ICI 联合治疗的患者（n = 18）中，ORR、DCR、mPFS 和 mOS 分别为 27.8%、100.0%、10.1 个月和 19.7 个月。PD-L1≥1%的患者 OS 明显优于 PD-L1<1%的患者（NA 与 11.7 个月， = 0.001）。在 19 例 mIHC 患者中，PD-1/PD-L1 和 LAG3 表达较高的患者 PFS 较长（19.0. 3.9 个月， = 0.003）。ICI 对治疗转移性 PLELC 也显示出良好的疗效。PD-L1 可能是预测 ICI 治疗疗效和 PLELC 生存的预后因素。PD-1/PD-L1 联合 LAG3 可能是预测 PLELC 中 ICI 治疗效果的指标。需要更大规模的前瞻性试验来验证 PLELC 中 ICI 的活性和预测生物标志物。本研究部分内容曾在 2019 年 9 月 7 日至 10 日于西班牙巴塞罗那举行的第 20 届国际肺癌研究协会世界肺癌大会上以海报形式展示。
