BACKGROUND Approximately 10% of patients with small cell lung cancer (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. METHODS We queried 2,512,042 medical records from a single institution to identify SCLC patients 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 PD-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. RESULTS We evaluated 145 SCLC patients: 55 with PNS (25 neurologic and 30 endocrinologic) and 90 controls. Patients with neurologic PNS experienced improved overall survival (OS) compared to patients with endocrinologic PNS and controls (median OS 24mo vs. 12mo vs. 13mo, 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. CONCLUSION Tumor tissue from patients with SCLC with neurologic PNS demonstrated increased tumor infiltrating lymphocytes and PD-1/PD-L1 interaction consistent with an inflamed tumor microenvironment.

中文翻译：

---

神经系统副肿瘤综合征小细胞肺癌患者预后改善和肿瘤浸润淋巴细胞增加

背景 大约 10% 的小细胞肺癌 (SCLC) 患者会出现副肿瘤综合征 (PNS)。神经性 PNS 被认为可以改善预后，我们假设这与肿瘤浸润淋巴细胞和免疫识别增加有关。方法我们查询了来自一个机构的 2,512,042 份医疗记录，以确定有和没有 PNS 的 SCLC 患者，并进行手动、回顾性图表审查。然后，我们对肿瘤进行了多重荧光免疫组织化学和自动定量分析（AQUA® 技术），以评估 CD3、CD4 和 CD8 T 细胞浸润和 PD-1/PD-L1 相互作用。比较了神经性 PNS、内分泌性 PNS 和没有 PNS 的对照组的 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果。结果 我们评估了 145 名 SCLC 患者：55 名患有 PNS（25 名神经性和 30 名内分泌性）和 90 名对照者。与内分泌性 PNS 患者和对照组相比，神经性 PNS 患者的总生存期 (OS) 有所提高（中位 OS 分别为 24 个月、12 个月和 13 个月）。在 145 名患者中，我们从 34 名患者中鉴定出足以进行 AQUA 分析的肿瘤组织。在这 34 名患者的 37 份标本中，与内分泌性 PNS 患者或对照组的肿瘤相比，神经性 PNS 患者的 T 细胞浸润增加（p=0.033）和 PD-1/PD-L1 相互作用（p=0.014）。