Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Vanderbilt University School of Medicine, Nashville, Tennessee.
J Thorac Oncol. 2019 Nov;14(11):1970-1981. doi: 10.1016/j.jtho.2019.05.042. Epub 2019 Jun 12.
Approximately 10% of patients with SCLC develop a paraneoplastic syndrome (PNS). Neurologic PNS are thought to improve prognosis, which we hypothesized is related to increased tumor-infiltrating lymphocytes and immune recognition.
We queried 2,512,042 medical records from a single institution to identify patients who have SCLC with and without PNS and performed manual, retrospective chart review. We then performed multiplexed fluorescence immunohistochemistry and automated quantitative analysis (AQUA Technology) on tumors to assess CD3, CD4, and CD8 T cell infiltrates and programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interactions. T cell infiltrates and PD-1/PD-L1 interaction scores were compared among patients with neurologic PNS, endocrinologic PNS, and a control group without PNS. Clinical outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards models.
We evaluated 145 SCLC patients: 55 with PNS (25 neurologic and 30 endocrinologic) and 90 controls. Patients with neurologic PNS experienced improved overall survival compared to patients with endocrinologic PNS and controls (median overall survival of 24 months versus 12 months versus 13 months, respectively). Of the 145 patients, we identified tumor tissue from 34 patients that was adequate for AQUA analysis. Among 37 specimens from these 34 patients, patients with neurologic PNS had increased T cell infiltrates (p = 0.033) and PD-1/PD-L1 interaction (p = 0.014) compared to tumors from patients with endocrinologic PNS or controls.
Tumor tissue from patients with SCLC with neurologic PNS showed increased tumor-infiltrating lymphocytes and PD-1/PD-L1 interaction consistent with an inflamed tumor microenvironment.
约 10%的小细胞肺癌（SCLC）患者会出现副肿瘤综合征（PNS）。据推测，神经 PNS 可改善预后，我们假设这与肿瘤浸润淋巴细胞（TIL）增加和免疫识别有关。
我们从一家机构的 2512042 份病历中进行了查询，以确定患有伴或不伴 PNS 的 SCLC 患者，并进行了手动、回顾性图表审查。然后，我们对肿瘤进行了多重荧光免疫组化和自动定量分析（AQUA 技术），以评估 CD3、CD4 和 CD8 T 细胞浸润和程序性死亡受体 1（PD-1）/程序性死亡配体 1（PD-L1）的相互作用。比较了伴有神经 PNS、内分泌 PNS 的患者与无 PNS 的对照组之间的 T 细胞浸润和 PD-1/PD-L1 相互作用评分。使用 Kaplan-Meier 方法和 Cox 比例风险模型分析临床结局。
我们评估了 145 例 SCLC 患者：55 例伴有 PNS（25 例神经 PNS 和 30 例内分泌 PNS）和 90 例对照组。与内分泌 PNS 和对照组相比，伴有神经 PNS 的患者的总生存期（OS）有所改善（中位 OS 分别为 24 个月、12 个月和 13 个月）。在 145 例患者中，我们从 34 例患者中确定了足够的肿瘤组织进行 AQUA 分析。在这 34 例患者的 37 个标本中，与内分泌 PNS 或对照组的肿瘤相比，伴有神经 PNS 的患者的 TIL 浸润增加（p=0.033），且 PD-1/PD-L1 相互作用增强（p=0.014）。
伴有神经 PNS 的 SCLC 患者的肿瘤组织显示出增加的肿瘤浸润淋巴细胞和 PD-1/PD-L1 相互作用，这与炎症性肿瘤微环境一致。
