对接受 PD-1 抑制剂治疗的晚期非小细胞肺癌患者进行的血清细胞因子分析揭示了 CXCL12 的预测标志物。

Serum cytokine analysis in a cohort of advanced non-small cell lung cancer treated with PD-1 inhibitors reveals predictive markers of CXCL12.

机构信息

Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.

Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

出版信息

Front Immunol. 2023 Jun 9;14:1194123. doi: 10.3389/fimmu.2023.1194123. eCollection 2023.

BACKGROUND

The circulating predictive factors for the outcomes of advanced non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs) remain elusive. We aimed to assess the predictive value of circulating cytokines for outcomes.

METHODS

Serum samples of 102 advanced-stage NSCLC patients who underwent immunotherapy were collected at baseline. The relative levels of 37 cytokines were detected. PD-L1 expression was also analyzed.

RESULTS

Higher serum CXCL12 levels (top 33%) were a poor predictive biomarker for durable clinical benefit (DCB) (23.5% vs. 72.1%, <0.001), progression-free survival (PFS) (3.76 vs. 14.40 months; <0.001) and overall survival (OS) (12.20 vs. 44.84 months; =0.008). Compared with PD-L1-negative patients, PD-L1-positive patients had a significantly higher objective response rate (ORR) (70.0% vs. 28.8%, <0.001) and a prolonged mPFS (25.35 vs. 4.64 months, =0.003) and tended to have an increased mOS (44.84 vs. 20.42 months, =0.087). A signature comprising PD-L1<1% and the top 33% CXCL12 level was associated with the lowest ORR (27.3% vs. 73.7%, <0.001) and DCB (27.3% vs. 73.7%, <0.001) and the worst mPFS (2.44 vs. 25.35 months, <0.001) and mOS (11.97 vs. 44.84 months, =0.007). Area under the curve (AUC) analyses of PD-L1 expression, CXCL12 level and PD-L1 expression plus CXCL12 level to predict DCB or no durable benefit (NDB) showed AUC values of 0.680, 0.719 and 0.794, respectively.

CONCLUSION

Our findings suggest that serum cytokine CXCL12 levels can predict the outcomes of patients with NSCLC receiving ICI. Moreover, the combination of CXCL12 levels and PD-L1 status can predict outcomes with a significantly improved discriminatory power.

背景

循环预测因子对于接受免疫检查点抑制剂（ICI）治疗的晚期非小细胞肺癌（NSCLC）患者的疗效仍然难以捉摸。我们旨在评估循环细胞因子对疗效的预测价值。

方法

收集 102 例接受免疫治疗的晚期 NSCLC 患者的基线血清样本。检测 37 种细胞因子的相对水平。还分析了 PD-L1 的表达。

结果

较高的血清 CXCL12 水平（前 33%）是持久临床获益（DCB）（23.5%比 72.1%，<0.001）、无进展生存期（PFS）（3.76 比 14.40 个月；<0.001）和总生存期（OS）（12.20 比 44.84 个月；=0.008）的不良预测生物标志物。与 PD-L1 阴性患者相比，PD-L1 阳性患者的客观缓解率（ORR）（70.0%比 28.8%，<0.001）更高，mPFS 更长（25.35 比 4.64 个月，=0.003），且 OS 有增加趋势（44.84 比 20.42 个月，=0.087）。由 PD-L1<1%和前 33% CXCL12 水平组成的特征与最低的 ORR（27.3%比 73.7%，<0.001）和 DCB（27.3%比 73.7%，<0.001）和最差的 mPFS（2.44 比 25.35 个月，<0.001）和 mOS（11.97 比 44.84 个月，=0.007）相关。PD-L1 表达、CXCL12 水平和 PD-L1 表达加 CXCL12 水平预测 DCB 或无持久获益（NDB）的 AUC 分析显示 AUC 值分别为 0.680、0.719 和 0.794。