The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, 210032, Jiangsu, China.
Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
Cancer Immunol Immunother. 2024 Jan 17;73(1):12. doi: 10.1007/s00262-023-03620-2.
The introduction of the anti-PD-1 antibody has greatly improved the clinical outcomes of patients with non-small cell lung cancer (NSCLC). In this study, we retrospectively analyzed the efficacy of PD-1 antibody-based therapy in patients with locally advanced inoperable or metastatic NSCLC and reported an association between peripheral blood biomarkers and clinical response in these patients.
This single-center study included medical record data of patients with NSCLC treated with the PD-1 antibody as a first-line or subsequent line of treatment, either as monotherapy or in combination with chemotherapy. The patients were enrolled from 2020 to 2022. We dynamically evaluated multiple Th1 and Th2 cytokines in the blood serum and analyzed the phenotype of T cells from the peripheral blood to explore the correlation between cytokine levels, T cell phenotypes, and clinical response.
A total of 88 patients with stage IIIA-IV NSCLC were enrolled, out of which 60 (68.18%) achieved a partial response (PR), 13 (14.77%) had stable disease (SD), and 15 (17.05%) experienced disease progression (PD). The disease control rate was 82.95%. Our results suggested a significant reduction (P = 0.002, P < 0.005) in lymphocyte absolute counts after treatment in patients with PD. Higher levels of IFN-γ (P = 0.023, P < 0.05), TNF-α (P = 0.00098, P < 0.005), IL-4 (P = 0.0031, P < 0.005), IL-5 (P = 0.0015, P < 0.005), and IL-10 (P = 0.036, P < 0.05) were detected in the peripheral blood before treatment in the PR group compared to the PD group. Moreover, patients with high levels of IL-5, IL-13, IL-4, IL-6, IFN-γ, and TNF-α (> 10 ng/mL) had superior progression-free survival compared to those with low levels (< 10 ng/mL). Furthermore, PD-1 expression on CD8 T cells was higher in patients who showed a PR than in those who did not show a response (SD + PD; P = 0.042, P < 0.05).
The findings of this study imply that the decrease in absolute blood lymphocyte counts after treatment is correlated with disease progression. Serum cytokine levels may predict the effectiveness and survival rates of anti-PD-1 blockade therapy in patients with NSCLC. In addition, PD-1 expression on CD8 T cells was positively associated with better clinical response. Our findings highlight the potential of peripheral blood biomarkers to predict the effectiveness of PD-1-targeted treatments in patients with NSCLC. Larger prospective studies are warranted to further clarify the value of these biomarkers.
抗 PD-1 抗体的引入极大地改善了非小细胞肺癌（NSCLC）患者的临床结局。在本研究中，我们回顾性分析了 PD-1 抗体在局部晚期不可切除或转移性 NSCLC 患者中的疗效，并报告了这些患者外周血生物标志物与临床反应之间的关联。
这项单中心研究纳入了接受 PD-1 抗体作为一线或二线治疗的 NSCLC 患者的病历数据，治疗方式包括单药治疗或联合化疗。患者于 2020 年至 2022 年入组。我们动态评估了血清中多种 Th1 和 Th2 细胞因子，并分析了外周血 T 细胞的表型，以探讨细胞因子水平、T 细胞表型与临床反应之间的相关性。
共纳入 88 例 IIIA-IV 期 NSCLC 患者，其中 60 例（68.18%）达到部分缓解（PR），13 例（14.77%）疾病稳定（SD），15 例（17.05%）疾病进展（PD）。疾病控制率为 82.95%。我们的结果表明，PD 患者治疗后淋巴细胞绝对计数显著下降（P=0.002，P<0.005）。PR 组患者治疗前外周血中 IFN-γ（P=0.023，P<0.05）、TNF-α（P=0.00098，P<0.005）、IL-4（P=0.0031，P<0.005）、IL-5（P=0.0015，P<0.005）和 IL-10（P=0.036，P<0.05）水平较高。此外，IL-5、IL-13、IL-4、IL-6、IFN-γ和 TNF-α水平较高（>10ng/mL）的患者无进展生存期优于水平较低（<10ng/mL）的患者。此外，与未发生反应（SD+PD）的患者相比，PR 患者的 CD8 T 细胞上的 PD-1 表达更高（P=0.042，P<0.05）。
本研究结果提示治疗后绝对血淋巴细胞计数的下降与疾病进展相关。血清细胞因子水平可能预测 NSCLC 患者抗 PD-1 阻断治疗的有效性和生存率。此外，CD8 T 细胞上的 PD-1 表达与更好的临床反应呈正相关。我们的发现强调了外周血生物标志物在预测 NSCLC 患者 PD-1 靶向治疗有效性方面的潜力。需要更大规模的前瞻性研究来进一步阐明这些生物标志物的价值。
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