转移性黑色素瘤易普利姆单抗治疗期间血浆蛋白动态:与肿瘤反应、不良事件和生存的关系

IF 6.5 2区 医学 Q1 IMMUNOLOGY
Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2024-12-19 DOI:10.1080/2162402X.2024.2440967
Ragnhild Reehorst Lereim, Claire Dunn, Elin Aamdal, Sudhir Kumar Chauhan, Oddbjørn Straume, Tormod Kyrre Guren, Jon Amund Kyte
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引用次数: 0

摘要

免疫检查点抑制剂ipilimumab在一些转移性黑色素瘤患者中提供长期生存,但大多数没有益处,并且可能出现严重的副作用。在这里,我们研究了血浆细胞因子浓度的动态及其在预测接受易普利姆单抗单药治疗的转移性黑色素瘤患者的治疗反应、不良事件和总生存期(OS)方面的潜在效用。对148名患者进行了队列检查,在治疗开始前和第一个和第二个治疗周期结束时收集血浆样本。采用多重免疫分析法测定48种血浆蛋白的浓度。结果显示,在第一次伊匹单抗剂量后,细胞因子水平普遍增加,与免疫激活一致。与肿瘤应答者相比,对治疗无反应的患者表现出G-CSF、IL-2RA、MIP-1a和SCF的基线水平显著升高(p < 0.05)
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival.

The immune checkpoint inhibitor ipilimumab provides long term survival in some metastatic melanoma patients, but the majority has no benefit, and may experience serious side effects. Here, we investigated the dynamics of plasma cytokine concentrations and their potential utility for predicting treatment response, adverse events and overall survival (OS) in patients with metastatic melanoma undergoing ipilimumab monotherapy. A cohort of 148 patients was examined, with plasma samples collected prior to treatment initiation and at the end of the first and second treatment cycles. Concentrations of 48 plasma proteins were measured using a multiplex immunoassay. The results revealed a general increase in cytokine levels following the first ipilimumab dose, consistent with immune activation. Patients not responding to treatment exhibited significantly elevated baseline levels of G-CSF, IL-2RA, MIP-1a, and SCF, compared to tumor responders (p < 0.05). Furthermore, high levels of IL-2RA, IFNγ, PDGF-bb and MIG were linked to inferior OS, while high concentrations of MIF and RANTES were associated with improved OS (p < 0.05). A multivariate model containing CRP, LDH, ECOG, IL-2RA and PDGF-bb identified a subgroup of patients with poor OS. Patients who experienced severe immune-related adverse events within three months of treatment initiation had higher baseline concentrations of several cytokines, indicating a potential association between preexisting inflammation and adverse events. These findings indicate that the first dose of ipilimumab induces a systemic response with increased levels of circulating cytokines and suggest candidate biomarkers for clinical response, immune-mediated toxicity and survival. Further studies in independent patient cohorts are required to confirm the findings.

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来源期刊
Oncoimmunology
Oncoimmunology ONCOLOGYIMMUNOLOGY-IMMUNOLOGY
CiteScore
12.50
自引率
2.80%
发文量
276
审稿时长
24 weeks
期刊介绍: OncoImmunology is a dynamic, high-profile, open access journal that comprehensively covers tumor immunology and immunotherapy. As cancer immunotherapy advances, OncoImmunology is committed to publishing top-tier research encompassing all facets of basic and applied tumor immunology. The journal covers a wide range of topics, including: -Basic and translational studies in immunology of both solid and hematological malignancies -Inflammation, innate and acquired immune responses against cancer -Mechanisms of cancer immunoediting and immune evasion -Modern immunotherapies, including immunomodulators, immune checkpoint inhibitors, T-cell, NK-cell, and macrophage engagers, and CAR T cells -Immunological effects of conventional anticancer therapies.
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