高级别浆液性卵巢癌患者治疗反应的新免疫表型。
New immune phenotypes for treatment response in high-grade serous ovarian carcinoma patients.
发表日期:2024
作者:
Cecilie Fredvik Torkildsen, Marie Austdal, Anders Hagen Jarmund, Katrin Kleinmanns, Eva Karin Lamark, Elisabeth Berge Nilsen, Ingunn Stefansson, Ragnar Kvie Sande, Ann-Charlotte Iversen, Liv Cecilie Vestrheim Thomsen, Line Bjørge
来源:
Frontiers in Immunology
摘要:
尽管手术和治疗方法取得了进步,但高级别浆液性卵巢癌(HGSOC)的预后仍然很差。手术是治疗方案中不可或缺的组成部分,因为切除所有可见的肿瘤病变(细胞减灭术)可以显着提高总体生存率。用于评估细胞减灭术的增强预测工具对于优化治疗精度至关重要。患者的免疫状态广泛反映了肿瘤细胞的生物学行为以及患者对疾病和治疗的反应。血清细胞因子分析是免疫适应和偏差的敏感测量方法,但其与治疗范式的整合尚未得到充分探索。这项研究是 IMPACT 试验 (NCT03378297) 的一部分,旨在表征 HGSOC 初级治疗之前和期间的免疫反应,以确定用于治疗选择和预后的生物标志物。从诊断到反应评估期间收集了 22 名患者的纵向血清样本。根据腹腔镜评分,患者接受了初次细胞减灭术或新辅助化疗(NACT)。 Bio-Plex 200 分析了 27 种血清细胞因子,在诊断时揭示了两种免疫表型:免疫高,血清细胞因子水平明显高于免疫低。免疫表型反映了腹腔镜评分和手术治疗的分配。与接受相同治疗的免疫低患者相比,接受初次细胞减灭术的五名免疫高患者表现出免疫动员和延长的无进展生存期。腹腔镜检查和细胞减灭术均引起血清细胞因子的显着和短暂变化,炎症细胞因子 IL-6 上调,多功能细胞因子 IP-10、Eotaxin、IL-4 和 IL-7 下调。在研究期间,所有患者的细胞因子水平一致下降,导致最初的免疫表型消失,无论治疗选择如何。这项研究揭示了 HGSOC 患者独特的治疗前免疫表型,这可能为治疗分层和预后提供信息。这种潜在的新型生物标志物有望成为改善 HGSOC 患者治疗反应评估的基础。 ClinicalTrials.gov 标识符:NCT03378297。版权所有 © 2024 Torkildsen、Austdal、Jarmund、Kleinmanns、Lamark、Nilsen、Stefansson、Sande、Iversen、Thomsen 和 Bjørge。
Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of therapeutic protocols, as removal of all visible tumor lesions (cytoreduction) profoundly improves the overall survival. Enhanced predictive tools for assessing cytoreduction are essential to optimize therapeutic precision. Patients' immune status broadly reflects the tumor cell biological behavior and the patient responses to disease and treatment. Serum cytokine profiling is a sensitive measure of immune adaption and deviation, yet its integration into treatment paradigms is underexplored. This study is part of the IMPACT trial (NCT03378297) and aimed to characterize immune responses before and during primary treatment for HGSOC to identify biomarkers for treatment selection and prognosis. Longitudinal serum samples from 22 patients were collected from diagnosis until response evaluation. Patients underwent primary cytoreductive surgery or neoadjuvant chemotherapy (NACT) based on laparoscopy scoring. Twenty-seven serum cytokines analyzed by Bio-Plex 200, revealed two immune phenotypes at diagnosis: Immune High with marked higher serum cytokine levels than Immune Low. The immune phenotypes reflected the laparoscopy scoring and allocation to surgical treatment. The five Immune High patients undergoing primary cytoreductive surgery exhibited immune mobilization and extended progression-free survival, compared to the Immune Low patients undergoing the same treatment. Both laparoscopy and cytoreductive surgery induced substantial and transient changes in serum cytokines, with upregulation of the inflammatory cytokine IL-6 and downregulation of the multifunctional cytokines IP-10, Eotaxin, IL-4, and IL-7. Over the study period, cytokine levels uniformly decreased in all patients, leading to the elimination of the initial immune phenotypes regardless of treatment choice. This study reveals distinct pre-treatment immune phenotypes in HGSOC patients that might be informative for treatment stratification and prognosis. This potential novel biomarker holds promise as a foundation for improved assessment of treatment responses in patients with HGSOC. ClinicalTrials.gov Identifier: NCT03378297.Copyright © 2024 Torkildsen, Austdal, Jarmund, Kleinmanns, Lamark, Nilsen, Stefansson, Sande, Iversen, Thomsen and Bjørge.