Romano Francesco Jacopo, Ronga Riccardo, Ambrosio Francesca, Arundine Dario, Longo Vito, Galetta Domenico, Gridelli Cesare, Maione Paolo, Palma Valentina, Damiano Vincenzo, Verde Antonio, Giacobbe Ilaria, Augurio Maria Rosaria, Iengo Gennaro, Chetta Massimiliano, Tarsitano Marina, Campione Severo, Failla Giuseppe, Raucci Antonio, Riccardi Ferdinando
Oncology Unit, "Antonio Cardarelli" Hospital, Naples, Italy.
Thoracic Oncology Unit, National Cancer Institute "Giovanni Paolo II", Bari, Italy.
Cancer Diagn Progn. 2023 Jan 3;3(1):44-52. doi: 10.21873/cdp.10178. eCollection 2023 Jan-Feb.
BACKGROUND/AIM: Lung cancer is one of the most common malignant neoplastic diseases and by far the leading cause of cancer death worldwide. Recently, immune checkpoint inhibitors (ICIs) have received increasing attention for playing a crucial role in non-small cell lung cancer (NSCLC). Biomarkers, such as programmed cell death-ligand 1 (PD-L1) and tumor mutational burden (TMB), seemed to be helpful in selecting patients who are more likely to benefit from ICI treatment: however, their role has not yet been fully clarified.
In this retrospective study, we evaluated the relationship between pre-treatment peripheral blood neutrophil-to-lymphocyte ratio (NLR) and survival in 252 patients suffering from advanced NSCLC who had received pembrolizumab as their first-line immunotherapy.
Compared to their NLR low counterparts who had a median overall survival (OS) of 34.8 months, patients with NLRs above 4.8 had a median OS of 7.6 months (HR=3.26, 95%Cl=2.3-4.6, p-value<0.0000001). In multivariate Cox regression analysis, alongside other variables, such as metastatic sites, age, and sex, NLR and PD-L1 predicted progression-free survival and OS; furthermore, a very high NLR - over 10 - seemed to forecast a very dismal prognosis in patients undergoing immunotherapy, with sudden deaths in the days immediately following therapy (median OS=3.8 months).
NLR acts as a valuable and reliable prognostic factor in non-small cell lung carcinoma patients undergoing first line immunotherapy with pembrolizumab. Additional investigation is necessary to fully elucidate the underlying biological rationale, which can be found in myeloid derived suppressor cells, a heterogeneous population of cells with neutrophil-like immunophenotypic features.
背景/目的：肺癌是最常见的恶性肿瘤疾病之一，也是目前全球癌症死亡的主要原因。近年来，免疫检查点抑制剂（ICI）在非小细胞肺癌（NSCLC）中发挥着关键作用，受到越来越多的关注。生物标志物，如程序性细胞死亡配体1（PD-L1）和肿瘤突变负荷（TMB），似乎有助于选择更可能从ICI治疗中获益的患者：然而，它们的作用尚未完全阐明。
在这项回顾性研究中，我们评估了252例接受派姆单抗作为一线免疫治疗的晚期NSCLC患者治疗前外周血中性粒细胞与淋巴细胞比值（NLR）与生存之间的关系。
NLR低于4.8的患者中位总生存期（OS）为34.8个月，而NLR高于4.8的患者中位OS为7.6个月（HR=3.26，95%CI=2.3-4.6，p值<0.0000001）。在多变量Cox回归分析中，与转移部位、年龄和性别等其他变量一起，NLR和PD-L1可预测无进展生存期和OS；此外，非常高的NLR（超过10）似乎预示着接受免疫治疗的患者预后非常差，在治疗后几天内会突然死亡（中位OS=3.8个月）。
NLR是接受派姆单抗一线免疫治疗的非小细胞肺癌患者有价值且可靠的预后因素。需要进一步研究以充分阐明其潜在的生物学原理，这可能与髓源性抑制细胞有关，髓源性抑制细胞是一群具有中性粒细胞样免疫表型特征的异质性细胞。
