原发性胰腺癌的免疫表型研究  

Research on immunophenotype of primary pancreatic cancer

作　　者：邱春燕 郑楷炼 张火俊 Qiu Chunyan;Zheng Kailian;Zhang Huojun(Department of Radiation Oncology, Changhai Hospital, Navy Medical University, Shanghai 200433, China;Department of General Surgery, Changhai Hospital, Navy Medical University, Shanghai 200433, China)

机构地区：[1]海军军医大学附属长海医院放疗科,上海200433 [2]海军军医大学附属长海医院普外科,上海200433

出　　处：《中华胰腺病杂志》2019年第2期91-97,共7页Chinese Journal of Pancreatology

基　　金：国家重点研发计划(2017YFC0113104).

摘　　要：目的全面分析原发性胰腺癌的免疫表型,为胰腺癌治疗提供生物学依据。方法纳入癌症基因组数据库中的177例原发性胰腺癌患者的基因组图谱,对样本进行总体免疫浸润(IIS)、T细胞浸润(TIS)和抗原呈递体系(APM)的量化评分。通过行无监督聚类分析,根据IIS、TIS和APM评分高低将患者分为免疫成分高组和免疫成分低组,比较两组免疫细胞亚型浸润、免疫检查点分子表达及免疫功能评价的差异。结果放疗人群中免疫成分高组生存率略高于免疫成分低组,但差异无统计学意义。与免疫成分低组比较,免疫成分高组具有明显较多的中性粒细胞(63.4%比36.6%)、嗜酸性粒细胞(75.5%比24.5%)、活化型CD4+记忆T淋巴细胞(80.7%比19.3%)、幼稚型CD4+T淋巴细胞(81.2%比18.8%)以及幼稚型B淋巴细胞(59.5%比40.5%);而免疫成分低组具有明显较多浸润的活化型NK细胞(67.3%比32.7%)、调节性T淋巴细胞(68.9%比31.1%)、辅助性滤泡T淋巴细胞(67.7%比32.3%)以及活化型肥大细胞(62.9%比37.1%)。与免疫成分高组比较,免疫成分低组的共刺激分子CD28、ICOS、CD40、CD40L、CD27、CD27L、4-1BB、OX40、GITR及共抑制分子CTLA-4、PD-L2、PD-1、VISTA、LAG-3、TIGIT、Galectin-9、TIM-3、IDO-1均显著高表达,差异均有统计学意义(P值均<0.05)。而免疫成分高组的趋化因子表达水平主成分分析的PC1值、细胞杀伤活性(CYT)值均显著高于免疫成分低组,差异有统计学意义(P值均<0.001)。结论利用3种免疫量化评分的聚类分析可对胰腺癌免疫表型初步分组,免疫成分高组可能与放疗具有协同作用。免疫检查点抑制剂治疗可能对免疫成分低组人群有效。Objective To comprehensively analyse the immunophenotype of primary pancreatic cancer, providing biological clues for treating pancreatic cancer. Methods The genome map of 177 primary pancreatic cancer patients from the Cancer Genome Atlas (TCGA) database were enrolled. The overall immune infiltration score (IIS), T cell infiltration score (TIS) and antigen presenting machinery (APM) score were quantified for each specimen. By using unsupervised clustering, the patients were divided into immune-high group and immune-low group according to IIS, TIS, and APM scores. The differences on the infiltration of immune cell subtype, expression of immune checkpoint and immunological function evaluation were compared between two groups. Results In the radiotherapy population, the survival rate of immune-high group was slightly higher than that of immune-low group with no statistical significance. The immune-high group had more infiltrated neutrophils (63.4% vs 36.6%), eosinophils (75.5% vs 24.5%), activated CD4+ memory T lymphocytes (80.7% vs 19.3%), naive CD4+ T lymphocytes (81.2% vs 18.8%) and naive B lymphocytes (59.5% vs 40.5%) compared with immune low group;while the immune-low group had more activated NK cells (67.3% vs 32.7%), regulatory T lymphocytes (68.9% vs 31.1%), T follicular helper (67.7% vs 32.3%), and activated mast cells (62.9% vs 37.1%). Co-stimulatory molecules such as CD28, ICOS, CD40, CD40L, CD27, CD27L, 4-1BB, OX40, GITR and co-inhibitory molecules including CTLA-4, PD-L2, PD-1, VISTA, LAG-3, TIGIT, Galectin-9, TIM-3, and IDO-1 were significantly higher expressed in the immune-low group (all P<0.05). The PC1 value of principal component analysis of chemokine expression levels and the cytolytic activity (CYT) in the immune-high group were significantly higher (all P<0.001). Conclusions Clustering on the three immune quantification scores could be preliminarily used for immunophenotyping pancreatic cancer. The immune-high group may have synergistic effect with radiation therapy. Treatment with immune chec

关 键 词：胰腺肿瘤 免疫表型分型 免疫检查点 佐剂 免疫 

分 类 号：R735.9[医药卫生—肿瘤]