Siemiątkowska Anna, Kuźnar-Kamińska Barbara, Bryl Maciej, Kosicka-Noworzyń Katarzyna, Przybył Paulina, Gołda-Gocka Iwona, Główka Franciszek K
Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806, Poznań, Poland.
Department of Pulmonology, Allergology and Respiratory Oncology, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569, Poznań, Poland.
Sci Rep. 2025 Apr 16;15(1):13078. doi: 10.1038/s41598-025-97792-9.
Cancer is a state of immunological imbalance associated with chronic inflammation and local immunosuppression. Introducing immune checkpoint inhibitors was a breakthrough in cancer treatment. However, the treatment outcomes remain unsatisfactory, and many patients still progress after the initial response. The study aimed to assess whether serum neopterin (NEO), an indicator of cellular immune activation, could be used as a predictor of the long-term benefits of drugs blocking the programmed cell death protein 1 pathway (anti-PD-1/PD-L1 drugs). We enrolled 103 patients with non-small cell lung cancer (NSCLC) treated with anti-PD-1/PD-L1s. Serum was collected at baseline and at the end of each treatment cycle for the first three months of immunotherapy. NEO concentrations were determined with a validated high-performance liquid chromatography assay and correlated with treatment outcomes. Low-NEO status (i.e., serum NEO levels ≤ 71.65 nM at the end of the 3rd treatment cycle and ≤ 66.84 nM at the end of the 4th treatment cycle) increased the odds of ≥ 12-month benefits (odds ratio, OR = 11.70, p < 0.001), and decreased the hazard of NSCLC progression (hazard ratio, HR = 0.327, p < 0.001) and treatment failure (adjusted HR = 0.450, p < 0.05). Patients with low-NEO status had three times longer progression-free survival (PFS, 17.3 vs. 5.9 months) and three times longer time to treatment failure (TTF, 16.3 vs. 5.5 months) compared to other patients. Baseline NEO levels could not discriminate between patients who had and lacked the long-term benefits of treatment. In conclusion, the on-treatment serum NEO concentrations could be a biomarker of the long-term benefits of the anti-PD-1/PD-L1 treatment in advanced NSCLC.
癌症是一种与慢性炎症和局部免疫抑制相关的免疫失衡状态。引入免疫检查点抑制剂是癌症治疗的一项突破。然而，治疗效果仍不尽人意，许多患者在初始反应后仍会病情进展。该研究旨在评估细胞免疫激活指标血清新蝶呤（NEO）是否可作为阻断程序性细胞死亡蛋白1通路的药物（抗PD-1/PD-L1药物）长期获益的预测指标。我们纳入了103例接受抗PD-1/PD-L1治疗的非小细胞肺癌（NSCLC）患者。在免疫治疗的前三个月，于基线期和每个治疗周期结束时采集血清。采用经过验证的高效液相色谱法测定NEO浓度，并将其与治疗结果相关联。低NEO状态（即第3个治疗周期结束时血清NEO水平≤71.65 nM，第4个治疗周期结束时≤66.84 nM）增加了≥12个月获益的几率（优势比，OR = 11.70，p < 0.001），并降低了NSCLC进展的风险（风险比，HR = 0.327，p < 0.001）和治疗失败的风险（校正HR = 0.450，p < 0.05）。与其他患者相比，低NEO状态的患者无进展生存期（PFS，17.3对5.9个月）和至治疗失败时间（TTF，16.3对5.5个月）延长了两倍。基线NEO水平无法区分有和没有治疗长期获益的患者。总之，治疗期间血清NEO浓度可能是晚期NSCLC患者抗PD-1/PD-L1治疗长期获益的生物标志物。
