不同的循环细胞因子/趋化因子谱与晚期非小细胞肺癌免疫检查点抑制剂单药治疗和联合治疗的临床获益相关。

BACKGROUND

An ever-increasing number of efforts are focused on identifying effective biomarkers for immune checkpoint inhibitors (ICIs). Cytokines and chemokines are critical to tumor growth, metastasis, tumor angiogenesis, and the immune response against tumor cells. In the study here, we determined the correlation between circulating cytokines/chemokines and the clinical benefit of ICIs for non-small cell lung cancer (NSCLC) patients.

METHODS

Peripheral blood samples were collected before and during treatment (at 12th week). Plasma levels of cytokines/chemokines and specific stress response markers were measured using the Bio-Plex Pro Human Cytokines Grp I Panel (27-plex), an APEX1 detection kit, and a human LAP(TGF-β1) immunoassay kit. A Mann-Whitney U-test or Wilcoxon signed-rank test and a Cox proportional hazards model were employed for statistical analysis.

RESULTS

In the ICI monotherapy cohort, a high level of IL-6 at pretreatment or an elevation of IL-6, IL-8, FGF2, CXCL10, CCR1, PDFGB, TNF, and APEX1 posttreatment was associated with poor progress-free survival (PFS). A posttreatment elevation (defined herein as change rate) of CXCL10 was also associated with poor overall survival (OS). In the combinational therapy group, a high level of IL-12, IL-17A, FGF2, VEGF, and APEX1 at pretreatment and an elevation of CCL2 posttreatment were associated with poor PFS. A high level of IL-9, FGF2, PDFGB, CCL4, TFGB, and APEX1 at pretreatment and an elevation of IL-13, CSF2, and CCL2 at posttreatment were associated with poor OS of patients receiving combination therapy.

CONCLUSIONS

The study here suggests that circulating cytokines/chemokines are feasible, noninvasive biomarkers for predicting clinical benefit of ICI treatment for NSCLC. Distinct circulating factor profiles were observed in individuals receiving ICI monotherapy or combination therapy.

背景

越来越多的研究致力于寻找免疫检查点抑制剂（ICI）的有效生物标志物。细胞因子和趋化因子对肿瘤的生长、转移、肿瘤血管生成以及对肿瘤细胞的免疫反应至关重要。在本研究中，我们确定了循环细胞因子/趋化因子与非小细胞肺癌（NSCLC）患者接受 ICI 治疗的临床获益之间的相关性。

方法

在治疗前（第 12 周）和治疗期间采集外周血样本。使用 Bio-Plex Pro 人类细胞因子 Grp I 试剂盒（27 个指标）、APEX1 检测试剂盒和人类 LAP（TGF-β1）免疫测定试剂盒测定血浆细胞因子/趋化因子和特定应激反应标志物的水平。采用 Mann-Whitney U 检验或 Wilcoxon 符号秩检验和 Cox 比例风险模型进行统计学分析。

结果

在 ICI 单药治疗队列中，治疗前高 IL-6 水平或治疗后 IL-6、IL-8、FGF2、CXCL10、CCR1、PDFGB、TNF 和 APEX1 升高与无进展生存期（PFS）较差相关。治疗后 CXCL10 的升高（定义为变化率）也与总生存期（OS）较差相关。在联合治疗组中，治疗前高 IL-12、IL-17A、FGF2、VEGF 和 APEX1 水平以及治疗后 CCL2 升高与 PFS 较差相关。治疗前高水平的 IL-9、FGF2、PDFGB、CCL4、TFGB 和 APEX1 以及治疗后高水平的 IL-13、CSF2 和 CCL2 与接受联合治疗的患者 OS 较差相关。