PD-L1 和 CD47 的共表达预测非小细胞肺癌的生存并为未来的双重靶向免疫治疗提供启示。
PD-L1 and CD47 co-expression predicts survival and enlightens future dual-targeting immunotherapy in non-small cell lung cancer.
机构信息
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
出版信息
Thorac Cancer. 2021 Jun;12(11):1743-1751. doi: 10.1111/1759-7714.13989. Epub 2021 May 12.
BACKGROUD
Recent studies have indicated that programmed cell death-ligand 1 (PD-L1) and cluster of differentiation 47 (CD47) play an essential role in tumor immune evasion and may serve as potential targets for combined immunotherapy. The aim of our study was to evaluate the PD-L1/CD47 expression status in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD), and explore its survival impact and relevance with the immune microenvironment.
METHODS
The specimens from 190 LUSC and 240 LUAD patients who underwent intent-to-treat surgeries were retrospectively collected for immunohistochemistry assays of PD-L1, CD47, cluster of differentiation 8 (CD8), and cluster of differentiation 68 (CD68).
RESULTS
A total of 96 (22.3%) and 296 (68.8%) cases were positive for PD-L1 and CD47 expression, respectively, and 80 (18.6%) of them demonstrated the co-expression of PD-L1/CD47. The rate of PD-L1/CD47 co-expression was 23.7% in LUSC, significantly higher than the 14.6% in LUAD (p = 0.018). The median overall survival (OS) for all patients was 55.9 months (range 2.0-146.0 months). The univariate analysis showed that patients with positive CD47 expression (LUSC p = 0.003, LUAD p = 0.036) and PD-L1/CD47 co-expression (LUSC p = 0.023, LUAD p = 0.004) exhibited significantly worse prognosis. The multivariate analysis demonstrated that PD-L1/CD47 co-expression was an independent prognostic factor for OS (LUSC hazard ratio [HR] 1.922, 95% CI 1.245-2.969, p = 0.003; LUAD HR 1.549, 95% CI 1.015-2.364, p = 0.043). PD-L1/CD47 co-expression was associated with high CD8-positive T-lymphocyte density in LUSC (p = 0.004) and LUAD (p = 0.043), and with high CD68-positive macrophage density in LUSC (p = 0.026).
CONCLUSIONS
PD-L1/CD47 co-expression was an independent prognostic factor for LUSC and LUAD patients and may serve as a potential predictive biomarker for combined dual-targeting immunotherapy.
背景
最近的研究表明，程序性细胞死亡配体 1（PD-L1）和分化群 47（CD47）在肿瘤免疫逃逸中发挥着重要作用，可能成为联合免疫治疗的潜在靶点。我们的研究旨在评估肺鳞状细胞癌（LUSC）和肺腺癌（LUAD）中 PD-L1/CD47 的表达状态，并探讨其与免疫微环境的生存影响和相关性。
方法
回顾性收集了 190 例 LUSC 和 240 例 LUAD 患者接受意向治疗手术的标本，进行 PD-L1、CD47、分化群 8（CD8）和分化群 68（CD68）的免疫组织化学检测。
结果
共有 96（22.3%）例和 296（68.8%）例 PD-L1 和 CD47 表达阳性，其中 80（18.6%）例同时表达 PD-L1/CD47。LUSC 中 PD-L1/CD47 共表达率为 23.7%，明显高于 LUAD 的 14.6%（p=0.018）。所有患者的中位总生存期（OS）为 55.9 个月（范围 2.0-146.0 个月）。单因素分析显示，CD47 表达阳性的患者（LUSC p=0.003，LUAD p=0.036）和 PD-L1/CD47 共表达的患者（LUSC p=0.023，LUAD p=0.004）预后明显较差。多因素分析表明，PD-L1/CD47 共表达是 OS 的独立预后因素（LUSC HR 1.922，95%CI 1.245-2.969，p=0.003；LUAD HR 1.549，95%CI 1.015-2.364，p=0.043）。PD-L1/CD47 共表达与 LUSC（p=0.004）和 LUAD（p=0.043）中 CD8 阳性 T 淋巴细胞密度较高以及 LUSC（p=0.026）中 CD68 阳性巨噬细胞密度较高有关。
结论
PD-L1/CD47 共表达是 LUSC 和 LUAD 患者的独立预后因素，可能成为联合双重靶向免疫治疗的潜在预测生物标志物。
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