Alina Miruna Grecea-Balaj, Olga Soritau, Ioana Brie, Maria Perde-Schrepler, Piroska Virag, Eva Fischer-Fodor, Nicolae Todor, Mihai Cenariu, Ioana Nedelea, Tudor Eliade Ciuleanu
{"title":"抗pd -1治疗下非小细胞肺癌和黑色素瘤的血清TNF -α、IL-10和IL-2轨迹和结局:来自单一中心的纵向真实世界证据","authors":"Alina Miruna Grecea-Balaj, Olga Soritau, Ioana Brie, Maria Perde-Schrepler, Piroska Virag, Eva Fischer-Fodor, Nicolae Todor, Mihai Cenariu, Ioana Nedelea, Tudor Eliade Ciuleanu","doi":"10.3390/cimb47090746","DOIUrl":null,"url":null,"abstract":"<p><p>This prospective single-center study examined associations between serum cytokines-TNF-α, IL-2, and IL-10-and outcomes in stage IV non-small cell lung cancer (NSCLC, <i>n</i> = 43) and melanoma (<i>n</i> = 15) patients treated with Nivolumab at the Oncology Institute in Cluj-Napoca, Romania. Cytokines were measured at baseline (NSCLC: <i>n</i> = 43; melanoma: <i>n</i> = 15), 3 months (NSCLC: <i>n</i> = 20; melanoma: <i>n</i> = 7), and 6 months (NSCLC: <i>n</i> = 10; melanoma: <i>n</i> = 5). Melanoma patients showed sustained IL-2 and TNF-α increases, while NSCLC patients displayed heterogeneous cytokine dynamics. In NSCLC, elevated IL-10 at 3 months correlated with shorter survival (ρ = -0.51, 95% CI -0.78 to -0.12, <i>p</i> = 0.022) and poorer response (ρ = -0.65, 95% CI -0.86 to -0.23, <i>p</i> = 0.002). TNF-α showed a borderline association with response (ρ = -0.44, 95% CI -0.74 to 0.01, <i>p</i> = 0.050). In melanoma, 3-month TNF-α was inversely associated with survival (ρ = -0.82, 95% CI -0.97 to -0.15, <i>p</i> = 0.023) and response (ρ = -0.90, 95% CI -0.99 to -0.39, <i>p</i> = 0.006). Strong inter-cytokine correlations were observed (NSCLC: TNF-α vs. IL-10, ρ = 0.60, 95% CI 0.19-0.82; melanoma: ρ = 0.93, 95% CI 0.44-0.99). Baseline cytokines had limited utility, particularly in melanoma due to the small sample size. The most informative finding was the association of elevated 3-month IL-10 with adverse outcomes in NSCLC. These results support the value of dynamic cytokine monitoring in immunotherapy and warrant validation in larger cohorts.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468888/pdf/","citationCount":"0","resultStr":"{\"title\":\"Serum TNF -α, IL-10 and IL-2 Trajectories and Outcomes in NSCLC and Melanoma Under Anti-PD-1 Therapy: Longitudinal Real-World Evidence from a Single Center.\",\"authors\":\"Alina Miruna Grecea-Balaj, Olga Soritau, Ioana Brie, Maria Perde-Schrepler, Piroska Virag, Eva Fischer-Fodor, Nicolae Todor, Mihai Cenariu, Ioana Nedelea, Tudor Eliade Ciuleanu\",\"doi\":\"10.3390/cimb47090746\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This prospective single-center study examined associations between serum cytokines-TNF-α, IL-2, and IL-10-and outcomes in stage IV non-small cell lung cancer (NSCLC, <i>n</i> = 43) and melanoma (<i>n</i> = 15) patients treated with Nivolumab at the Oncology Institute in Cluj-Napoca, Romania. Cytokines were measured at baseline (NSCLC: <i>n</i> = 43; melanoma: <i>n</i> = 15), 3 months (NSCLC: <i>n</i> = 20; melanoma: <i>n</i> = 7), and 6 months (NSCLC: <i>n</i> = 10; melanoma: <i>n</i> = 5). Melanoma patients showed sustained IL-2 and TNF-α increases, while NSCLC patients displayed heterogeneous cytokine dynamics. In NSCLC, elevated IL-10 at 3 months correlated with shorter survival (ρ = -0.51, 95% CI -0.78 to -0.12, <i>p</i> = 0.022) and poorer response (ρ = -0.65, 95% CI -0.86 to -0.23, <i>p</i> = 0.002). TNF-α showed a borderline association with response (ρ = -0.44, 95% CI -0.74 to 0.01, <i>p</i> = 0.050). In melanoma, 3-month TNF-α was inversely associated with survival (ρ = -0.82, 95% CI -0.97 to -0.15, <i>p</i> = 0.023) and response (ρ = -0.90, 95% CI -0.99 to -0.39, <i>p</i> = 0.006). Strong inter-cytokine correlations were observed (NSCLC: TNF-α vs. IL-10, ρ = 0.60, 95% CI 0.19-0.82; melanoma: ρ = 0.93, 95% CI 0.44-0.99). 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引用次数: 0
摘要
这项前瞻性单中心研究检查了在罗马尼亚克卢日纳波卡肿瘤研究所接受Nivolumab治疗的IV期非小细胞肺癌(NSCLC, n = 43)和黑色素瘤(n = 15)患者血清细胞因子tnf -α、IL-2和il -10与预后之间的关系。在基线(NSCLC: n = 43;黑色素瘤:n = 15)、3个月(NSCLC: n = 20;黑色素瘤:n = 7)和6个月(NSCLC: n = 10;黑色素瘤:n = 5)时测量细胞因子。黑色素瘤患者表现出持续的IL-2和TNF-α升高,而非小细胞肺癌患者表现出异质性的细胞因子动力学。在非小细胞肺癌中,3个月时IL-10升高与较短的生存期(ρ = -0.51, 95% CI -0.78至-0.12,p = 0.022)和较差的反应(ρ = -0.65, 95% CI -0.86至-0.23,p = 0.002)相关。TNF-α与反应呈临界相关(ρ = -0.44, 95% CI -0.74 ~ 0.01, p = 0.050)。在黑色素瘤中,3个月TNF-α与生存率(ρ = -0.82, 95% CI -0.97至-0.15,p = 0.023)和疗效(ρ = -0.90, 95% CI -0.99至-0.39,p = 0.006)呈负相关。观察到很强的细胞因子间相关性(NSCLC: TNF-α vs. IL-10, ρ = 0.60, 95% CI 0.19-0.82;黑色素瘤:ρ = 0.93, 95% CI 0.44-0.99)。由于样本量小,基线细胞因子的效用有限,特别是在黑色素瘤中。最具信息量的发现是3个月IL-10升高与NSCLC不良结局的关联。这些结果支持动态细胞因子监测在免疫治疗中的价值,并需要在更大的队列中进行验证。
Serum TNF -α, IL-10 and IL-2 Trajectories and Outcomes in NSCLC and Melanoma Under Anti-PD-1 Therapy: Longitudinal Real-World Evidence from a Single Center.
This prospective single-center study examined associations between serum cytokines-TNF-α, IL-2, and IL-10-and outcomes in stage IV non-small cell lung cancer (NSCLC, n = 43) and melanoma (n = 15) patients treated with Nivolumab at the Oncology Institute in Cluj-Napoca, Romania. Cytokines were measured at baseline (NSCLC: n = 43; melanoma: n = 15), 3 months (NSCLC: n = 20; melanoma: n = 7), and 6 months (NSCLC: n = 10; melanoma: n = 5). Melanoma patients showed sustained IL-2 and TNF-α increases, while NSCLC patients displayed heterogeneous cytokine dynamics. In NSCLC, elevated IL-10 at 3 months correlated with shorter survival (ρ = -0.51, 95% CI -0.78 to -0.12, p = 0.022) and poorer response (ρ = -0.65, 95% CI -0.86 to -0.23, p = 0.002). TNF-α showed a borderline association with response (ρ = -0.44, 95% CI -0.74 to 0.01, p = 0.050). In melanoma, 3-month TNF-α was inversely associated with survival (ρ = -0.82, 95% CI -0.97 to -0.15, p = 0.023) and response (ρ = -0.90, 95% CI -0.99 to -0.39, p = 0.006). Strong inter-cytokine correlations were observed (NSCLC: TNF-α vs. IL-10, ρ = 0.60, 95% CI 0.19-0.82; melanoma: ρ = 0.93, 95% CI 0.44-0.99). Baseline cytokines had limited utility, particularly in melanoma due to the small sample size. The most informative finding was the association of elevated 3-month IL-10 with adverse outcomes in NSCLC. These results support the value of dynamic cytokine monitoring in immunotherapy and warrant validation in larger cohorts.
期刊介绍:
Current Issues in Molecular Biology (CIMB) is a peer-reviewed journal publishing review articles and minireviews in all areas of molecular biology and microbiology. Submitted articles are subject to an Article Processing Charge (APC) and are open access immediately upon publication. All manuscripts undergo a peer-review process.