晚期非小细胞肺癌患者长期无进展生存获益于免疫检查点抑制剂的临床及动态循环细胞因子谱特征

Clinical and dynamic circulating cytokines profile features of long-term progression-free survival benefit to immune checkpoint inhibitors in advanced non-small cell lung cancer.

作者信息

Deng Jia-Yi, Gao Ming, Fan Xue, Yan Hong-Hong, Luo Wei-Chi, Yang Ming-Yi, Yang Xiao-Rong, Chen Zhi-Hong, Xu Chong-Rui, Zhou Qing

机构信息

School of Medicine, South China University of Technology, Guangzhou, 510006, People's Republic of China.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China.

出版信息

Cancer Immunol Immunother. 2025 Apr 17;74(6):173. doi: 10.1007/s00262-025-03984-7.

DOI:10.1007/s00262-025-03984-7

PMID:40244472

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12006652/

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) offer durable progression-free survival (PFS) benefit in a subset of patients with advanced non-small cell lung cancer (NSCLC). However, the predictors of long-term PFS (LTPFS) remain unclear.

METHODS

Advanced NSCLC patients receiving first-line ICIs monotherapy at Guangdong Lung Cancer Institute between December 2017 and August 2022 were identified. Predictive value of different characteristics was evaluated in LTPFS (PFS ≥ 24 months) compared with short-term PFS (STPFS, PFS ≤ 3 months). Circulating cytokine levels were evaluated in paired peripheral blood samples collected before and after ICIs treatment.

RESULTS

Among 202 patients identified and 171 included (median follow-up: 41.0 months), 44 (25.7%) experienced LTPFS, associated with a 5-year overall survival (OS) rate of 81.2%. Squamous NSCLC, intermediate or poor lung immune prognostic index (LIPI) score, and liver metastases, were negatively associated with LTPFS. High tumor mutational burden (TMB, ≥ 10 mutations/megabase) was enriched in LTPFS compared to STPFS (P = 0.002). Patients with both high TMB and PD-L1 demonstrated the greatest survival benefit from first-line ICIs monotherapy (median PFS: 24.5 months, median OS: 67.0 months). Thirty-eight peripheral blood samples were collected before and after ICIs treatment from 10 patients with LTPFS and 9 with STPFS, which revealed increased CCL11 (P = 0.013) and decreased IL1RA (P = 0.001) and IL17A (P = 0.003) levels in LTPFS after ICIs treatment.

CONCLUSION

Distinct clinical characteristics, including TMB, PD-L1, pathologic subtypes, LIPI score, number of organs involved, metastatic sites, and dynamic circulating cytokines profile features, can distinguish NSCLC patients achieving LTPFS from those with STPFS following first-line ICIs monotherapy.

摘要

背景

免疫检查点抑制剂（ICI）在一部分晚期非小细胞肺癌（NSCLC）患者中可带来持久的无进展生存期（PFS）获益。然而，长期PFS（LTPFS）的预测因素仍不明确。

方法

确定2017年12月至2022年8月在广东省肺癌研究所接受一线ICI单药治疗的晚期NSCLC患者。评估不同特征在LTPFS（PFS≥24个月）与短期PFS（STPFS，PFS≤3个月）中的预测价值。在ICI治疗前后采集的配对外周血样本中评估循环细胞因子水平。

结果

在确定的202例患者中，171例纳入研究（中位随访时间：41.0个月），44例（25.7%）经历了LTPFS，5年总生存率（OS）为81.2%。鳞状NSCLC、肺免疫预后指数（LIPI）评分为中等或较差以及肝转移与LTPFS呈负相关。与STPFS相比，LTPFS中高肿瘤突变负荷（TMB，≥10个突变/兆碱基）更为富集（P = 0.002）。高TMB和PD-L1均阳性的患者从一线ICI单药治疗中获得的生存获益最大（中位PFS：24.5个月，中位OS：67.0个月）。从10例LTPFS患者和9例STPFS患者中在ICI治疗前后采集了38份外周血样本，结果显示ICI治疗后LTPFS患者中CCL11水平升高（P = 0.013），IL1RA（P = 0.001）和IL17A（P = 0.003）水平降低。