Leibniz Research Centre for Working Environment and Human Factors (IfADo) at TU Dortmund University, Dortmund, Germany.
Department of Statistics, TU Dortmund University, Dortmund, Germany.
J Thorac Oncol. 2019 Apr;14(4):628-640. doi: 10.1016/j.jtho.2018.12.022. Epub 2019 Jan 9.
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.
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.
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.
Proliferation, PD-L1 status, smoking history, and histology should be considered if lymphocyte infiltration is to be used as a prognostic biomarker.
浸润的 T 细胞和 B/浆细胞与非小细胞肺癌（NSCLC）的预后相关，但这在与程序性死亡配体 1（PD-L1）的表达的关系上尚未得到彻底研究。在这里，我们在两个未接受针对 PD-1/PD-L1 轴的检查点抑制剂治疗的接受手术的 NSCLC 患者的回顾性队列中，确定淋巴细胞和 PD-L1 与总生存期（OS）的相关性。此外，我们评估 PD-L1 阳性和临床病理因素如何影响淋巴细胞的预后相关性。
通过免疫组织化学在组织微阵列上测定簇分化（CD）3（CD3）-、CD8-、CD4-、叉头框 P3（FOXP3）-、CD20-、CD79A-和免疫球蛋白 κ 恒定（IGKC）-阳性免疫细胞，以及肿瘤 PD-L1 阳性（n=705）。对患者亚组进行 Affymetrix 数据分析，并补充公开可用的转录组数据（n=1724）。通过 Kaplan-Meier 图和单变量和多变量 Cox 回归评估与 OS 的相关性。
较高水平的 T 和 B 浆细胞与更长的 OS 相关（p=0.004 和 p<0.001，分别为 CD8 和 IGKC）。增殖能力高而淋巴细胞少的肿瘤预后最差。在未分层的患者人群中，未观察到 PD-L1 阳性与 OS 的相关性；然而，在从不吸烟者中观察到与较短 OS 的显著相关性（p=0.009 和 p=0.002，5%和 50%截止值）。在 PD-L1 阳性肿瘤中，淋巴细胞浸润与 OS 无关（50%截止值）。淋巴细胞浸润的预后相关性也取决于患者的吸烟史和组织学亚型。
如果要将淋巴细胞浸润用作预后生物标志物，则应考虑增殖、PD-L1 状态、吸烟史和组织学。
