Background: The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses.
Methods: We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed.
Results: All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline.
Conclusions: Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.
【中文题目：外周血免疫指标在肺癌患者免疫治疗中 的预测价值】 【中文摘要：背景与目的 免疫治疗的应用大大改善了肺癌患者的临床结局。很大一部分肺癌患者能从程序性死亡受体1（programmed cell death 1, PD-1）/程序性死亡配体1（programmed cell death ligand 1, PD-L1）单抗治疗中获益，然而，仍有一部分耐药患者疗效不佳，临床上迫切需要能早期、便捷识别获益人群的生物标志物。在此，本研究回顾性分析了PD-1抗体治疗对局部晚期无法手术或转移性肺癌患者的疗效，并初步探索了外周血免疫指标与患者临床反应的相关性。方法 该单中心研究共纳入2020年3月至2021年12月接受PD-1/PD-L1抗体治疗的IIIA-IV期肺癌患者61例，收集PD-1/PD-L1抗体一线或后线治疗的病历数据。检测并分析患者外周血血清中多重Th1和Th2细胞因子水平以及外周血T细胞表型，探索细胞因子水平、T细胞表型等和患者临床反应之间的关系。结果 入组患者均完成至少2个周期PD-1/PD-L1单抗治疗。其中，42例（68.9%）患者获得部分缓解（partial response, PR），7例（11.5%）患者疾病稳定（stable disease, SD），12例（19.7%）患者疾病进展（progressive disease, PD）。治疗前，疾病控制（disease control rate, DCR）组（有效组）患者外周血干扰素γ（interferon gamma, IFN-γ）（P=0.023）、肿瘤坏死因子α（tumor necrosis factor α, TNF-α）（P=0.007）和白介素5（interleukin 5, IL-5）（P=0.002）水平高于PD组（无效组）患者。此外，PD-1/PD-L1抗体治疗后外周血淋巴细胞绝对计数的减少与疾病进展有关联（P=0.023）。治疗后血清中IL-5（P=0.0027）和IL-10（P=0.0208）水平较治疗前明显升高。结论 肺癌患者外周血血清IFN-γ、TNF-α和IL-5水平在预测抗PD-1阻断治疗临床疗效方面有一定的作用，肺癌患者外周血淋巴细胞绝对计数的减少与疾病进展有一定相关性，还需要大型前瞻性研究进一步阐明这些生物标志物的价值。 】 【中文关键词：肺肿瘤；免疫治疗；生物标志物；疗效预测】.
Keywords: Biomarkers; Efficacy prediction; Immunotherapy; Lung neoplasms.