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Prognostic Impact of tumor cell PD-L1 expression and immune cell infiltration in NSCLC
Journal of Thoracic Oncology ( IF 20.4 ) Pub Date : 2019-04-01 , DOI: 10.1016/j.jtho.2018.12.022
Karolina Edlund 1 , Katrin Madjar 2 , Johanna S M Mattsson 3 , Dijana Djureinovic 3 , Cecilia Lindskog 3 , Hans Brunnström 4 , Hirsh Koyi 5 , Eva Brandén 5 , Karin Jirström 4 , Fredrik Pontén 3 , Jörg Rahnenführer 2 , Patrick Micke 3 , Jan G Hengstler 1
Affiliation  

Introduction: Infiltration of T and B/plasma cells has been linked to NSCLC prognosis, but this has not been thoroughly investigated in relation to the expression of programmed death ligand 1 (PD‐L1). Here, we determine the association of lymphocytes and PD‐L1 with overall survival (OS) in two retrospective cohorts of operated NSCLC patients who were not treated with checkpoint inhibitors targeting the programmed death 1/PD‐L1 axis. Moreover, we evaluate how PD‐L1 positivity and clinicopathologic factors affect the prognostic association of lymphocytes. Methods: Cluster of differentiation (CD) 3 (CD3)‐, CD8‐, CD4‐, forkhead box P3 (FOXP3)‐, CD20‐, CD79A‐, and immunoglobulin kappa constant (IGKC)‐positive immune cells, and tumor PD‐L1 positivity, were determined by immunohistochemistry on tissue microarrays (n = 705). Affymetrix data was analyzed for a patient subset, and supplemented with publicly available transcriptomics data (N = 1724). Associations with OS were assessed by Kaplan‐Meier plots and uni‐ and multivariate Cox regression. Results: Higher levels of T and B plasma cells were associated with longer OS (p = 0.004 and p < 0.001, for CD8 and IGKC, respectively). Highly proliferative tumors with few lymphocytes had the worst outcome. No association of PD‐L1 positivity with OS was observed in a nonstratified patient population; however, a significant association with shorter OS was observed in never‐smokers (p = 0.009 and p = 0.002, 5% and 50% cutoff). Lymphocyte infiltration was not associated with OS in PD‐L1–positive tumors (50% cutoff). The prognostic association of lymphocyte infiltration also depended on the patients’ smoking history and histologic subtype. Conclusions: Proliferation, PD‐L1 status, smoking history, and histology should be considered if lymphocyte infiltration is to be used as a prognostic biomarker.

中文翻译:

NSCLC中肿瘤细胞PD-L1表达和免疫细胞浸润的预后影响

简介:T 和 B/浆细胞的浸润与 NSCLC 预后有关,但尚未就程序性死亡配体 1 (PD-L1) 的表达进行彻底研究。在这里,我们确定了淋巴细胞和 PD-L1 与未接受靶向程序性死亡 1/PD-L1 轴的检查点抑制剂治疗的两个回顾性非小细胞肺癌手术患者队列的总生存期 (OS) 的关联。此外,我们评估了 PD-L1 阳性和临床病理因素如何影响淋巴细胞的预后关联。方法:分化簇 (CD) 3 (CD3)-、CD8-、CD4-、叉头盒 P3 (FOXP3)-、CD20-、CD79A- 和免疫球蛋白 kappa 常数 (IGKC) 阳性免疫细胞和肿瘤 PD- L1 阳性,通过组织微阵列上的免疫组织化学确定(n = 705)。Affymetrix 数据针对患者子集进行了分析,并补充了公开可用的转录组学数据(N = 1724)。通过 Kaplan-Meier 图和单变量和多变量 Cox 回归评估与 OS 的关联。结果:较高水平的 T 和 B 浆细胞与较长的 OS 相关(对于 CD8 和 IGKC,分别为 p = 0.004 和 p < 0.001)。淋巴细胞很少的高度增殖性肿瘤的结果最差。在非分层患者人群中未观察到 PD-L1 阳性与 OS 相关;然而,在从不吸烟者中观察到与较短的 OS 显着相关(p = 0.009 和 p = 0.002,5% 和 50% 截断值)。在 PD-L1 阳性肿瘤中,淋巴细胞浸润与 OS 无关(50% 截断值)。淋巴细胞浸润的预后关联还取决于患者的吸烟史和组织学亚型。结论:如果将淋巴细胞浸润用作预后生物标志物,应考虑增殖、PD-L1 状态、吸烟史和组织学。
更新日期:2019-04-01
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