卵巢癌免疫细胞浸润模式及其临床意义  

Patterns of Immunocyte Infiltration in Ovarian Cancer and Their Clinical Significance

作　　者：曹铁凤 黄佳明[1] 何雨诗 沈慧敏[1] CAO Tiefeng;HUANG Jiaming;HE Yushi(Department of Gynecology,The First Affiliated Hospital,Sun Yat-sen University,Guangdong 510080,China)

机构地区：[1]中山大学附属第一医院妇科,广州510080

出　　处：《医学研究杂志》2024年第6期29-34,共6页Journal of Medical Research

基　　金：国家自然科学基金青年科学基金资助项目(82002734);广东省基础与应用基础研究基金区域联合基金青年基金资助项目(2019A1515110312)。

摘　　要：目的探讨卵巢癌中免疫细胞浸润模式及对临床结局和化疗反应的影响。方法从公共数据库TCGA和GEO中下载2206例卵巢癌患者的临床资料和基因表达谱,使用反卷积算法(CIBERSORT)评估22种免疫细胞分布,以及其对总生存和化疗反应的影响。无监督聚类法将病例聚类,分析亚组之间临床结果的差异。采用从中山大学附属第一医院妇科收集的临床病例标本荧光染色对巨噬细胞浸润进行验证。结果幼稚B细胞、M2型巨噬细胞和静息记忆CD4^(+)T细胞与不良预后显著相关,而滤泡辅助性T细胞与良好预后显著相关。浆细胞、M1型巨噬细胞及活化记忆CD4^(+)T细胞与化疗敏感相关,M2型巨噬细胞与化疗耐药相关。无监督聚类确定了3个亚组,表现为巨噬细胞及T细胞不同分布比例,亚组之间总生存差异显著。卵巢癌转移组织中巨噬细胞浸润多于原发肿瘤。结论卵巢癌中免疫细胞浸润与临床预后及化疗耐药相关。免疫细胞靶向治疗或联合化疗可能是卵巢癌潜在治疗新模式。Objective To explore the patterns of the immunocyte infiltration in ovarian cancer,and their influence on clinical outcome and chemotherapy response.Methods The clinical information and gene expression profiles of 2206 ovarian cancer patients were downloaded from TCGA and GEO publicly databases.The CIBERSORT was used to evaluate the distribution of 22 immune cells and their effects on survival,and chemotherapy response.Unsupervised clustering was used to classify cases and analyze differences in clinical outcomes between subgroups.Immunofluorescence staining was performed to illustrate the macrophages infiltration in ovarian cancer samples collected from the First Affiliated Hospital,Sun Yat-sen University.Results Naive B cells,M2 macrophages,and resting memory CD4^(+)T cells were significantly associated with poor prognosis,while follicular helper T cells were significantly associated with good prognosis.Plasma cells,M1 macrophages,and activated memory CD4^(+)T cells were associated with chemotherapy sensitivity,and M2 macrophages were associated with chemotherapy resistant.Furthermore,three subgroups were identified by unsupervised clustering which showed different distribution ratios of macrophages and T cells,and significant differences in overall survival among subgroups.The infiltration of macrophages in metastasis tissue of ovarian cancer was more than that in primary tumor.Conclusion The immunocyte infiltration in ovarian cancer is associated with clinical prognosis and chemotherapy resistance.Immune cell targeting therapy or combination chemotherapy may be the potential treatment choices for ovarian cancer.

关 键 词：免疫浸润 反卷积 卵巢癌 临床结局 化疗反应 

分 类 号：R737[医药卫生—肿瘤]