Department of Pulmonary and Critical Care Medicine, Peking Union Medical Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Front Immunol. 2022 Jul 1;13:912180. doi: 10.3389/fimmu.2022.912180. eCollection 2022.
Non-small cell lung cancer (NSCLC) has entered the era of immunotherapy. However, only partial patients were able to benefit from immune checkpoint inhibitors (ICIs). Currently, biomarkers for predicting patients' response to ICIs are primarily tumor tissue dependent and have limited accuracy. There is an urgent need to explore peripheral blood-based biomarkers to predict the efficacy and safety of ICI therapy.
To explore the correlation between lymphocyte subsets and the efficacy and safety of ICIs, we retrospectively analyzed peripheral blood lymphocyte subsets and survival prognosis data of 136 patients with stage IV NSCLC treated with ICIs.
The two factors that had the greatest impact on the prognosis of patients with NSCLC treated with ICIs were CD4CD45RA T cell (HR = 0.644, P = 0.047) and CD8 T/lymphocyte (%) (HR = 1.806, P = 0.015). CD4CD45RA T cell showed excellent predictive efficacy (AUC = 0.854) for ICIs monotherapy, with a sensitivity of 75.0% and specificity of 91.7% using CD4CD45RA T cell >311.3 × 10/L as the threshold. In contrast, CD8 T/lymphocyte (%) was only associated with the prognosis but had no predictive role for ICI efficacy. CD4 T cell and its subsets were significantly higher in patients with mild (grades 1-2) immune-related adverse events (irAEs) than those without irAEs. CD8CD38 T cell was associated with total irAEs and severe (grades 3-4) irAEs but was not suitable to be a predictive biomarker.
Peripheral blood CD4CD45RA T cell was associated with the prognosis of patients with NSCLC applying ICIs, whereas CD8CD38 T cell was associated with irAEs and severe irAEs.
非小细胞肺癌（NSCLC）已进入免疫治疗时代。然而，只有部分患者能从免疫检查点抑制剂（ICIs）中获益。目前，预测患者对 ICIs 反应的生物标志物主要依赖于肿瘤组织，且准确性有限。因此，迫切需要探索基于外周血的生物标志物来预测 ICI 治疗的疗效和安全性。
为了探讨淋巴细胞亚群与 NSCLC 患者接受 ICI 治疗的疗效和安全性之间的相关性，我们回顾性分析了 136 例接受 ICIs 治疗的 IV 期 NSCLC 患者的外周血淋巴细胞亚群和生存预后数据。
对 NSCLC 患者接受 ICI 治疗的预后影响最大的两个因素是 CD4CD45RA T 细胞（HR=0.644，P=0.047）和 CD8 T/淋巴细胞（%）（HR=1.806，P=0.015）。CD4CD45RA T 细胞对 ICIs 单药治疗具有优异的预测效果（AUC=0.854），当以 CD4CD45RA T 细胞>311.3×10/L 作为阈值时，其灵敏度为 75.0%，特异性为 91.7%。相比之下，CD8 T/淋巴细胞（%）仅与预后相关，而对 ICI 疗效无预测作用。发生轻（1-2 级）度免疫相关不良事件（irAEs）的患者的 CD4 T 细胞及其亚群明显高于未发生 irAEs 的患者。CD8CD38 T 细胞与总 irAEs 和重度（3-4 级）irAEs 相关，但不适合作为预测生物标志物。
外周血 CD4CD45RA T 细胞与 NSCLC 患者接受 ICI 治疗的预后相关，而 CD8CD38 T 细胞与 irAEs 和重度 irAEs 相关。
