Background/Objectives: Endometriosis and high-grade serous ovarian cancer (HGS-OC) share common features within the peritoneal immune microenvironment, yet they exhibit divergent clinical outcomes. This study aimed to dissect the immune–metabolic landscape of the peritoneal cavity in patients with endometriosis and ovarian cancer by evaluating macrophage polarization, intracellular signaling pathways, and iron-driven oxidative stress. Methods: A prospective cohort study enrolled 40 patients with endometriosis, 198 with ascitic ovarian cancer (178 HGS-OC), and 200 controls with benign gynecological conditions. Peritoneal and peripheral blood samples were analyzed via flow cytometry for macrophage (M1/M2) polarization markers, mTOR/AKT expression, and glucose uptake. Inflammatory markers (IL-6, CRP), oxidative stress (ROS), and iron metabolism parameters (hepcidin, ferritin, transferrin, serum/free iron) were quantified. Results: HGS-OC displayed a predominance of M1-polarized tumor-associated macrophages (TAMs) (CD14⁺/CD80⁺/Glut1⁺) and a high M1/M2 ratio (2.5 vs. 0.8 and 0.9;p= 0.019), correlating positively with IL-6 (p= 0.015), ROS (p= 0.023), hepcidin (p= 0.038), and ferritin (p= 0.043). Conversely, endometriosis showed a dominant M2 profile (CD14⁺/CD163⁺), elevated intracellular mTOR and AKT expression in both TAMs and epithelial cells (p< 0.01), and significantly higher ascitic ROS and free iron levels (p= 0.047 andp< 0.0001, respectively). In endometriosis, the M1/M2 ratio correlated inversely with free iron (p= 0.041), while ROS levels were directly associated with iron overload (p= 0.0034). Conclusions: Endometriosis exhibits a distinct immune–metabolic phenotype characterized by M2 macrophage predominance and iron-induced oxidative stress, contrasting with the inflammatory, M1-rich profile of HGS-OC. These findings suggest that iron metabolism and macrophage plasticity contribute to disease persistence in endometriosis and may inform future immunomodulatory strategies.
**背景/目的：** 子宫内膜异位症与高级别浆液性卵巢癌在腹膜免疫微环境中具有共同特征，但临床结局迥异。本研究旨在通过评估巨噬细胞极化、细胞内信号通路及铁驱动氧化应激，剖析子宫内膜异位症与卵巢癌患者腹腔的免疫-代谢特征。 **方法：** 一项前瞻性队列研究纳入了40例子宫内膜异位症患者、198例腹水性卵巢癌患者（其中178例为高级别浆液性癌）以及200例良性妇科疾病对照者。通过流式细胞术分析腹腔及外周血样本中的巨噬细胞（M1/M2）极化标志物、mTOR/AKT表达及葡萄糖摄取。定量检测炎症标志物（IL-6、CRP）、氧化应激（ROS）及铁代谢参数（铁调素、铁蛋白、转铁蛋白、血清/游离铁）。 **结果：** 高级别浆液性卵巢癌显示出以M1极化的肿瘤相关巨噬细胞为主（CD14⁺/CD80⁺/Glut1⁺），且M1/M2比值较高（2.5 vs. 0.8 和 0.9；p=0.019），该比值与IL-6（p=0.015）、ROS（p=0.023）、铁调素（p=0.038）及铁蛋白（p=0.043）呈正相关。相反，子宫内膜异位症表现为以M2表型为主（CD14⁺/CD163⁺），肿瘤相关巨噬细胞和上皮细胞中细胞内mTOR和AKT表达均升高（p<0.01），且腹水ROS和游离铁水平显著更高（分别为p=0.047和p<0.0001）。在子宫内膜异位症中，M1/M2比值与游离铁呈负相关（p=0.041），而ROS水平与铁过载直接相关（p=0.0034）。 **结论：** 子宫内膜异位症表现出独特的免疫-代谢表型，其特征为M2巨噬细胞占优势和铁诱导的氧化应激，这与高级别浆液性卵巢癌富含M1的炎症性特征形成对比。这些发现表明，铁代谢和巨噬细胞可塑性促进了子宫内膜异位症的疾病持续存在，并可能为未来的免疫调节策略提供信息。
Divergent Immune–Metabolic Profiles in Endometriosis and Ovarian Cancer: A Cross-Sectional Analysis
肿瘤(癌症)患者之家