Li Ji-Wei, Wei Ping, Guo Ye, Shi Di, Yu Bao-Hua, Su Yi-Fan, Li Xiao-Qiu, Zhou Xiao-Yan
Department of Pathology, Fudan University Shanghai Cancer Center Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University Shanghai 200032, China.
Am J Cancer Res. 2020 Dec 1;10(12):4498-4512. eCollection 2020.
Exosomal PD-L1 (exoPD-L1) is reported to be associated with immunosuppression in various cancers. However, its clinical value in extranodal NK/T cell lymphoma (ENKTL) has not been defined yet. We retrospectively evaluated the prognostic value of pretreatment circulating soluble PD-L1 (sPD-L1) and exosomal PD-L1 (exoPD-L1) in ENKTL patients treated with VIPD-containing chemotherapy. A total of 107 ENKTL patients, including 101 early stage and 6 advanced stage patients were enrolled in our study. ExoPD-L1 and sPD-L1 in the blood were measured by single molecule array (Simoa) and enzyme-linked immunosorbent assay (ELISA), respectively. Compared with the healthy individuals (n=16), the patients with ENKTL (n=107) exhibited significantly elevated exoPD-L1 and sPD-L1 levels in the blood. High pretreatment plasma exoPD-L1 concentration was associated with higher SUVmax level and recurrence rate. Similarly, high sPD-L1 group was also associated with some adverse clinical parameters, including advanced stage, elevated LDH levels, B symptoms, high IPI score and PINK score. The 5-year progression-free survival (PFS) rate and overall survival (OS) rates were 65.2% and 85.7% for the whole cohort, respectively. Patients with a low pretreatment exoPD-L1 level (simoa signal < 1.2) had 5-year OS and PFS rates of 88.1% and 86.1%, respectively, compared with 56.0%. (P=0.012) and 35.7% (P=0.007) in patients with high exoPD-L1 level (simoa signal > 1.2). The 5-year OS and PFS rates for patients with low sPD-L1 group (< 219 pg/mL) was significantly higher than high sPD-L1 group (≥ 219 pg/mL) (OS, 91.3% vs. 55.5%, P < 0.001; PFS, 68.9% vs. 34.6%, P=0.003). However, no correlation was found between circulating exoPD-L1 and sPD-L1 levels. This is the first study to measure plasma exoPD-L1 level on the Quanterix Simoa platform. Our results proved that circulating exoPD-L1 and sPD-L1 levels were significantly elevated in ENKTL and might be potential biomarkers for predicting the survival outcomes of ENKTL patients.
据报道，外泌体程序性死亡受体配体1（exoPD-L1）与多种癌症的免疫抑制有关。然而，其在结外NK/T细胞淋巴瘤（ENKTL）中的临床价值尚未明确。我们回顾性评估了含VIPD化疗的ENKTL患者预处理时循环可溶性PD-L1（sPD-L1）和外泌体PD-L1（exoPD-L1）的预后价值。我们的研究共纳入了107例ENKTL患者，包括101例早期患者和6例晚期患者。分别采用单分子阵列（Simoa）和酶联免疫吸附测定（ELISA）检测血液中的ExoPD-L1和sPD-L1。与健康个体（n = 16）相比，ENKTL患者（n = 107）血液中的exoPD-L1和sPD-L1水平显著升高。预处理时血浆exoPD-L1浓度高与SUVmax水平高和复发率高相关。同样，高sPD-L1组也与一些不良临床参数相关，包括晚期、乳酸脱氢酶水平升高、B症状、高国际预后指数（IPI）评分和PINK评分。整个队列的5年无进展生存率（PFS）和总生存率（OS）分别为65.2%和85.7%。预处理时exoPD-L1水平低（Simoa信号<1.2）的患者5年OS率和PFS率分别为88.1%和86.1%，而exoPD-L1水平高（Simoa信号>1.2）的患者分别为56.0%（P = 0.012）和35.7%（P = 0.007）。低sPD-L1组（<219 pg/mL）患者的5年OS和PFS率显著高于高sPD-L1组（≥219 pg/mL）（OS，91.3%对55.5%，P<0.001；PFS，68.9%对34.6%，P = 0.003）。然而，循环exoPD-L1和sPD-L1水平之间未发现相关性。这是第一项在Quanterix Simoa平台上检测血浆exoPD-L1水平的研究。我们的结果证明，ENKTL患者循环exoPD-L1和sPD-L1水平显著升高，可能是预测ENKTL患者生存结果的潜在生物标志物。
