Wang Yida, Chen Hanxiao, Zhang Tianzhuo, Yang Xue, Zhong Jia, Wang Yuyan, Chi Yujia, Wu Meina, An Tongtong, Li Jianjie, Zhao Xinghui, Dong Zhi, Wang Ziping, Zhao Jun, Zhuo Minglei, Huang Jing
Department of Immunology, School of Basic Medical Sciences, Peking University, and NHC Key Laboratory of Medical Immunology (Peking University), Beijing, China.
Key Laboratory of Molecular Immunology, Chinese Academy of Medical Sciences, Beijing, China.
Ann Transl Med. 2021 Jan;9(1):33. doi: 10.21037/atm-20-1513.
Although programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint inhibitors have shown prominent efficacy for treatment of advanced lung cancer, the outcomes of metastatic lung cancer remain poor throughout the world. Although progression-free survival (PFS) and overall survival (OS) have improved in the first- and second-line therapy settings for advanced lung cancer, the response rates to PD-1/PD-L1 inhibition range from 20% to 40%. Furthermore, patients may be at risk for immune-related adverse events (irAEs); hence, appropriate patient selection is crucial. This study aimed to identify a panel of plasma cytokines representing prognostic and predictive biomarkers of the response to anti-PD-1/PD-L1 treatment.
We prospectively studied 32 lung cancer patients who received anti-PD-1/PD-L1 antibody immunotherapy. Plasma cytokines in peripheral blood samples were evaluated and analyzed using flow cytometry at the time of diagnosis and at 2 months after the initiation of PD-1/PD-L1 inhibition.
The baseline plasma concentrations of interleukin-18 (IL-18) and C-X-C motif chemokine ligand 10 (CXCL10) were correlated with the degree of tumor response. Moreover, the magnitude of plasma IL-18 and CXCL10 level fluctuations were correlated significantly with the objective tumor response to anti-PD-1/PD-L1 immunotherapy, and patients with high CXCL10 expression had significantly shorter PFS than those with low CXCL10 expression. A strong positive correlation between the fluctuation of IL-18 and interleukin-8 (IL-8) levels was detected, as was a negative correlation between the fluctuation of IL-18 and CXCL10 levels. The level of plasma C-C motif chemokine ligand 5 (CCL5) was significantly higher in patients with irAEs than in those without irAEs.
Plasma cytokines are related to the clinical efficacy of PD-1/PD-L1 inhibitors. IL-18 and CXCL10 are potential predictive markers for anti-PD-1/PD-L1 therapy in lung cancer patients and may play an important role in selecting patients who would benefit from PD-1/PD-L1 inhibitors.
尽管程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）检查点抑制剂已显示出对晚期肺癌治疗的显著疗效，但转移性肺癌在全球范围内的治疗效果仍然较差。虽然晚期肺癌一线和二线治疗中的无进展生存期（PFS）和总生存期（OS）有所改善，但PD-1/PD-L1抑制的缓解率在20%至40%之间。此外，患者可能有发生免疫相关不良事件（irAE）的风险；因此，合适的患者选择至关重要。本研究旨在确定一组血浆细胞因子，作为抗PD-1/PD-L1治疗反应的预后和预测生物标志物。
我们前瞻性地研究了32例接受抗PD-1/PD-L1抗体免疫治疗的肺癌患者。在诊断时以及开始PD-1/PD-L1抑制治疗2个月后，使用流式细胞术对外周血样本中的血浆细胞因子进行评估和分析。
白细胞介素-18（IL-18）和C-X-C基序趋化因子配体10（CXCL10）的基线血浆浓度与肿瘤反应程度相关。此外，血浆IL-18和CXCL10水平波动幅度与抗PD-1/PD-L1免疫治疗的客观肿瘤反应显著相关，CXCL10高表达患者的PFS显著短于CXCL10低表达患者。检测到IL-18与白细胞介素-8（IL-8）水平波动之间存在强正相关，IL-18与CXCL10水平波动之间存在负相关。发生irAE的患者血浆C-C基序趋化因子配体5（CCL5）水平显著高于未发生irAE的患者。
血浆细胞因子与PD-1/PD-L1抑制剂的临床疗效相关。IL-18和CXCL10是肺癌患者抗PD-1/PD-L1治疗的潜在预测标志物，可能在选择将从PD-1/PD-L1抑制剂中获益的患者方面发挥重要作用。
