PDF(Pubmed)
Abstract：
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.
摘要：
尽管手术和治疗方法取得了进展，高级别浆液性卵巢癌（HGSOC）预后仍然较差。手术是治疗方案不可或缺的组成部分，因为去除所有可见的肿瘤病变（细胞减少）极大地改善了总体生存率。用于评估细胞减少的增强的预测工具对于优化治疗精度至关重要。患者的免疫状态大致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。血清细胞因子谱是免疫适应和偏差的敏感测量，然而，它与治疗范式的整合还没有得到充分的探索。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，以确定治疗选择和预后的生物标志物。从诊断直到反应评估收集来自22名患者的纵向血清样品。患者接受基于腹腔镜评分的原发性细胞减灭术或新辅助化疗（NACT）。Bio-Plex200分析的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的评分和手术治疗的分配。接受原发性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，与接受相同治疗的免疫低下患者相比。腹腔镜和细胞减灭术均可引起血清细胞因子的实质性和一过性变化，随着炎症细胞因子IL-6的上调和多功能细胞因子IP-10，Eotaxin的下调，IL-4和IL-7。在学习期间，所有患者的细胞因子水平均下降，导致消除初始免疫表型，无论治疗选择如何。这项研究揭示了HGSOC患者治疗前不同的免疫表型，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作为改善HGSOC患者治疗反应评估的基础。ClinicalTrials.gov标识符：NCT03378297。
