Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Mexico City, Mexico.
Global Medical Affairs Oncology, AstraZeneca, Gaithersburg, USA.
Cancer Immunol Immunother. 2018 Sep;67(9):1393-1406. doi: 10.1007/s00262-018-2196-y. Epub 2018 Jul 4.
Polymorphonuclear-MDSC (PMN-MDSC) have emerged as an independent prognostic factor for survival in NSCLC. Similarly, cytokine profiles have been used to identify subgroups of NSCLC patients with different clinical outcomes. This prospective study investigated whether the percentage of circulating PMN-MDSC, in conjunction with the levels of plasma cytokines, was more informative of disease progression than the analysis of either factor alone. We analyzed the phenotypic and functional profile of peripheral blood T-cell subsets (CD3, CD3CD4 and CD3CD8), neutrophils (CD66b) and polymorphonuclear-MDSC (PMN-MDSC; CD66bCD11bCD15CD14-) as well as the concentration of 14 plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IL-27, IL-29, IL-31, and IL-33, TNF-α, IFN-γ) in 90 treatment-naïve NSCLC patients and 25 healthy donors (HD). In contrast to HD, NSCLC patients had a higher percentage of PMN-MDSC and neutrophils (P < 0.0001) but a lower percentage of CD3, CD3CD4 and CD3CD8 cells. PMN-MDSC% negatively correlated with the levels of IL1-β, IL-2, IL-27 and IL-29. Two groups of patients were identified according to the percentage of circulating PMN-MDSC. Patients with low PMN-MDSC (≤ 8%) had a better OS (22.1 months [95% CI 4.3-739.7]) than patients with high PMN-MDSC (9.3 months [95% CI 0-18.8]). OS was significantly different among groups of patients stratified by both PMN-MDSC% and cytokine levels. In sum, our findings provide evidence suggesting that PMN-MDSC% in conjunction with the levels IL-1β, IL-27, and IL-29 could be a useful strategy to identify groups of patients with potentially unfavorable prognoses.
中性粒细胞-髓系来源抑制细胞 (PMN-MDSC) 已成为 NSCLC 患者生存的独立预后因素。同样,细胞因子谱已被用于鉴定具有不同临床结局的 NSCLC 患者亚组。这项前瞻性研究调查了循环 PMN-MDSC 的百分比与血浆细胞因子水平结合使用是否比单独分析任一因素更能反映疾病进展情况。我们分析了外周血 T 细胞亚群(CD3、CD3CD4 和 CD3CD8)、中性粒细胞(CD66b)和中性粒细胞-髓系来源抑制细胞(PMN-MDSC;CD66bCD11bCD15CD14-)的表型和功能谱,以及 14 种血浆细胞因子(IL-1β、IL-2、IL-4、IL-6、IL-8、IL-10、IL-12 p70、IL-17A、IL-27、IL-29、IL-31 和 IL-33、TNF-α、IFN-γ)的浓度,在 90 例未经治疗的 NSCLC 患者和 25 名健康供体(HD)中进行了分析。与 HD 相比,NSCLC 患者的 PMN-MDSC 和中性粒细胞百分比更高(P<0.0001),但 CD3、CD3CD4 和 CD3CD8 细胞百分比更低。PMN-MDSC%与 IL1-β、IL-2、IL-27 和 IL-29 的水平呈负相关。根据循环 PMN-MDSC 的百分比将患者分为两组。PMN-MDSC 水平较低(≤8%)的患者的 OS(22.1 个月[95%CI 4.3-739.7])优于PMN-MDSC 水平较高(9.3 个月[95%CI 0-18.8])的患者。根据 PMN-MDSC%和细胞因子水平分层的患者组之间的 OS 存在显著差异。总之,我们的研究结果提供了证据表明,PMN-MDSC%与 IL-1β、IL-27 和 IL-29 的水平相结合可能是一种有用的策略,可以识别具有潜在不良预后的患者组。