| 摘要: |
| 目的 通过研究不同同源重组缺陷（HRD）状态的晚期卵巢癌中免疫细胞和细胞因子的表达差异性，为卵巢癌的治疗提供新的思路。方法 选取上海交通大学医学院附属瑞金医院妇产科2018年1月至2023年1月收治的68例国际妇产科联盟（FIGO）分期为Ⅲ～Ⅳ期的上皮来源卵巢癌患者，依据基因检测结果将其分为HRD阳性组（n＝30）和HRD阴性组（n＝38），比较两组患者的一般资料和临床疗效。采用免疫组织化学染色分析两组患者卵巢癌组织中CD4、CD8、CD25的表达情况，采用流式细胞技术分析血液中CD4+ T细胞、CD8+ T细胞、CD4+CD25+调节性T细胞（Treg细胞）的比例及CD4+/CD8+比值。采用ELISA法检测血清中干扰素γ、IL-2、IL-6、IL-10水平。结果 HRD阳性组和HRD阴性组患者在年龄、病程、家族史、初始治疗方式、肿瘤FIGO分期、肿瘤分化程度方面的差异均无统计学意义（均P＞0.05）。在临床疗效方面，HRD阳性组患者的客观缓解率和疾病控制率均高于HRD阴性组患者，差异均有统计学意义（均P＜0.05）。与HRD阴性组相比，HRD阳性组患者肿瘤组织中CD4、CD8、CD25的表达量均增加（均P＜0.05）；血液中CD4+ T细胞、CD8+ T细胞、CD4+CD25+ Treg细胞比例均增加（均P＜0.05），CD4+/CD8+比值升高（P＜0.05）；血清中IL-2、IL-6、IL-10水平均升高（均P＜0.05），而干扰素γ水平在两组间差异无统计学意义（P＞0.05）。结论 相较于HRD阴性卵巢癌患者，HRD阳性卵巢癌患者的肿瘤组织中有更多的免疫细胞浸润，分泌更多有免疫调节作用的细胞因子。HRD阳性卵巢癌患者可能对免疫治疗更敏感，预后也较好。 |
| 关键词: 卵巢肿瘤 同源重组缺陷 肿瘤微环境 免疫细胞 细胞因子 |
| DOI：10.16781/j.CN31-2187/R.20240822 |
| 投稿时间：2024-12-04修订日期：2025-03-06 |
| 基金项目:国家自然科学基金（82002724），上海市嘉定区卫生健康委员会科研课题（2022-KY-24）． |
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| Analysis of immune cell and cytokine expression differences in advanced ovarian cancer based on homologous recombination deficiency status |
| BAO Qingyue,LU Xiaolan,FENG Weiwei,CUI Xiaojuan* |
(Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
*Corresponding author) |
| Abstract: |
| Objective To analyze the expression differences in immune cells and cytokines in advanced ovarian cancer with different homologous recombination deficiency (HRD) statuses, and provide insights for novel therapeutic strategies. Methods A total of 68 patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅲ-Ⅳ epithelial ovarian cancer, who were treated at Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from Jan. 2018 to Jan. 2023, were enrolled. Based on genetic testing results, patients were stratified into HRD-positive (n＝30) and HRD-negative (n＝38) groups. Baseline characteristics and clinical outcomes were compared. The expression levels of CD4, CD8 and CD25 in ovarian cancer tissues of the 2 groups were analyzed by immunohistochemical staining. The proportions of CD4+ T cells, CD8+ T cells, and CD4+CD25+ regulatory T cells (Treg cells) and CD4+/CD8+ ratio in blood were analyzed by flow cytometry. The serum levels of interferon-γ (IFN-γ), interleukin (IL)-2, IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay. Results There were no significant differences in age, course of disease, family history, initial treatment, tumor FIGO stage, or tumor differentiation degree between the HRD-positive group and HRD-negative group (all P＞0.05). In terms of clinical efficacy, the objective remission rate and disease control rate of patients in the HRD-positive group were significantly higher than those in the HRD-negative group (both P＜0.05). Compared with the HRD-negative group, the expression levels of CD4, CD8, and CD25 in tumor tissues of patients were all increased in the HRD-positive group (all P＜0.05), the proportions of CD4+ T cells, CD8+ T cells, and CD4+CD25+ Treg cells in blood were all increased (all P＜0.05), the CD4+/CD8+ ratio in blood was increased (P＜0.05), the serum levels of IL-2, IL-6, and IL-10 were all increased (all P＜0.05), while the serum level of IFN-γ had no significant difference between the 2 groups (P＞0.05). Conclusion HRD-positive ovarian cancer displays enhanced tumor-infiltrating lymphocytes and immunomodulatory cytokine secretion compared to HRD-negative cases, suggesting greater sensitivity to immunotherapy and better prognosis. |
| Key words: ovarian neoplasms homologous recombination deficiency tumor microenvironment immune cells cytokines |
