欧阳燕,张世超,贾义,胡祖权,王赟,周静,刘丽娜,唐福州,曾柱
OUYANG Yan,ZHANG Shichao,JIA Yi,HU Zuquan,WANG Yun,ZHOU Jing,LIU Lina,TANG Fuzhou,ZENG Zhu

• 1:贵州医科大学生物与医学工程重点实验室
• 2:贵州医科大学生物与工程学院
• 3:贵州医科大学基础医学院

摘要(Abstract)：

目的:研究胃癌中免疫细胞的浸润模式,探究浸润的免疫细胞与肿瘤预后的关系。方法:对375个非转移性胃癌患者肿瘤样本的基因表达数据进行计算分析,通过CIBERSORT软件计算22种免疫细胞类型的比例,用Cox回归模型评估肿瘤中浸润性免疫细胞与总生存期(OS)之间的关系。结果:375例胃癌患者肿瘤组织中巨噬细胞(31. 9%)、未活化的CD4+记忆性T细胞(16. 5%)、CD8 T细胞(13. 5%)、调节性T细胞(6. 8%)比较丰富,随着胃癌患者肿瘤分期的增加,γδT细胞和M2巨噬细胞的比例逐渐上升,而活化的自然杀伤细胞和M0巨噬细胞的比例逐渐降低;较高水平的滤泡辅助性T细胞与胃癌患者较长的OS相关,而较高比例的M2巨噬细胞、单核细胞和未活化的树突状细胞与较差OS相关。结论:肿瘤中浸润性免疫细胞的组成在胃癌各个分期中存在较大的差异,浸润性免疫细胞可以作为肿瘤独立的预后因子。
Objective: To investigate the infiltration pattern of immunocyte in gastric cancer and relationship between tumor prognosis and infiltrating immunocyte. Methods: Analyses on gene expression profiles of 375 tumor samples of nonmetastatic gastric cancer patients were performed. CIBERSORT was applied to estimate the fraction of 22 immunocyte types,Cox regression model was adopted to evaluate relation between infiltrating immunocyte in tumor and overall survival(OS). Results: 375 cases of gastric cancer tissue showed results of macrophage(31. 9%),non-activated CD4 + memory T cells(16. 5%),CD8 T cells(13. 5%),regulating T cell(6. 8%) were abundant. With the increase in tumor stage of gastric cancer,the fraction of γδ T cells and M2 macrophages increased; whereas the fraction of activated natural killer cells and M0 macrophages decreased. Higher level of folliculus auxiliary T cells were related to longer OS in gastric cancer patients,while higher fractions of M2 macrophages,monocytes and resting dendritic cells were related to worse OS. Conclusion: The composition of tumor-infiltrating immunocyte differed greatly in different stages of gastric cancer and tumor-infiltrating immunocyte can be used as independent prognostic factors.

关键词(KeyWords)： 胃癌;免疫细胞;肿瘤浸润;预后;免疫治疗
gastric cancer;immunocyte;tumor infiltrating;prognosis;immunotherapy

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(31660258,31771014,11762006);; 贵州省科技计划项目[黔科合基础(2018)1412,黔科合平台人才(2016)5676,黔科合人才团队(2015)4021];; 2011协同创新中心[黔教合协同创新字(2015)04];; 贵州省细胞与基因工程创新群体[黔教合KY字(2016)031];; 贵州医科大学博士启动基金(YJ2017-10)

作者(Author): 欧阳燕,张世超,贾义,胡祖权,王赟,周静,刘丽娜,唐福州,曾柱
OUYANG Yan,ZHANG Shichao,JIA Yi,HU Zuquan,WANG Yun,ZHOU Jing,LIU Lina,TANG Fuzhou,ZENG Zhu

DOI: 10.19367/j.cnki.1000-2707.2018.11.005

参考文献(References)：

• [1]BUI Q L,GRAZZIOTIN-SOARES D,HASINIATSY R E,et al. Metastatic stomach cancer:Clinical trials in Asia and in Occident[J]. Bull Cancer,2018,18:30233-30239.
• [2]ARNOLD M,MOORE S P,HASSLER S,et al. The burden of stomach cancer in indigenous populations:a systematic review and global assessment[J]. Gut,2014,63(1):64-71.
• [3]NOTO J M,PEEK RM,J R. The gastric microbiome,its interaction with Helicobacter pylori,and its potential role in the progression to stomach cancer[J]. PLo S Pathog,2017,13(10):e1006573.
• [4]YOSHIZAWA N,YAMAGUCHI H,KAMINISHI M. Differential diagnosis of solitary gastric Peutz-Jeghers-type polyp with stomach cancer:a case report[J]. Int J Surg Case Rep,2018,51:261-264.
• [5] SCHADENDORF D,HODI F S,ROBERT C,et al.Pooled Analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma[J]. J Clin Oncol,2015,33(17):1889-1894.
• [6] LOTE H,CAFFERKEY C,CHAU I. PD-1 and PD-L1blockade in gastrointestinal malignancies[J]. Cancer Treat Rev,2015,41(10):893-903.
• [7] DAVIDSON M,OKINES A F,STARLING N. Current and future therapies for advanced gastric cancer[J]. Clin Colorectal Cancer,2015,14(4):239-250.
• [8]NEWMAN A M,LIU C L,GREEN M R,et al. Robust enumeration of cell subsets from tissue expression profiles[J]. Nat Methods,2015,12(5):453-457.
• [9]CHAROENTONG P,FINOTELLO F,ANGELOVA M,et al. Pan-cancer immunogenomic analyses reveal genotypeimmunophenotype relationships and predictors of response to checkpoint blockade[J]. Cell Rep,2017,18(1):248-262.
• [10]BINDEA G,MLECNIK B,TOSOLINI M,et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer[J]. Immunity,2013,39(4):782-795.
• [11]ALI H R,CHLON L,PHAROAH P D,et al. Patterns of immune infiltration in breast cancer and their clinical implications:A gene-expression-based retrospective study[J]. PLo S Med,2016,13(12):e1002194.
• [12]ROHR-UDILOVA N,KLINGLMULLER F,SCHULTEHERMANN R,et al. Deviations of the immune cell landscape between healthy liver and hepatocellular carcinoma[J]. Sci Rep,2018,8(1):6220.
• [13]ZHU Y,QIU P,JI Y. TCGA-assembler:open-source software for retrieving and processing TCGA data[J]. Nat Methods,2014,11(6):599-600.
• [14]CHANMEE T,ONTONG P,KONNO K,et al. Tumorassociated macrophages as major players in the tumor microenvironment[J]. Cancers(Basel),2014,6(3):1670-1690.
• [15]RHEE I. Diverse macrophages polarization in tumor microenvironment[J]. Arch Pharm Res,2016,39(11):1588-1596.
• [16]LIU X,WU S,YANG Y,et al. The prognostic landscape of tumor-infiltrating immune cell and immunomodulators in lung cancer[J]. Biomed Pharmacother,2017,95:55-61.
• [17]BENSE R D,SOTIRIOU C,PICCART-GEBHART M J,et al. Relevance of tumor-infiltrating immune Cell composition and functionality for disease outcome in breast cancer[J]. Journal of the National Cancer Institute,2017,109(1):djw192.
• [18]ZHANG R,QI CF,HU Y,et al. T follicular helper cells restricted by IRF8 contribute to T cell-mediated inflammation[J]. Journal of autoimmunity,2018,18:30287-30287.
• [19]PENNINGTON D J,SILVA-SANTOS B,HAYDAY A C.Gammadelta T cell development--having the strength to get there[J]. Curr Opin Immunol,2005,17(2):108-115.
• [20]GENTLES A J,NEWMAN A M,LIU C L,et al. The prognostic landscape of genes and infiltrating immune cells across human cancers[J]. Nat Med,2015,21(8):938-945.
• [21]LO PRESTI E,PIZZOLATO G,GULOTTA E,et al.Current advances in gammadelta T cell-based tumor immunotherapy[J]. Front Immunol,2017,8:1401.
• [22]LI C,LUO X,LIN Y,et al. A Higher frequency of CD14+CD169+monocytes/macrophages in patients with colorectal cancer[J]. PLo S One,2015,10(10):e0141817.

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