title: Accumulation Mechanisms of CD4(+)CD25(+)FOXP3(+) Regulatory T Cells in EBV-associated Gastric Carcinoma.
abstract: Approximately 10% of gastric carcinomas are associated with Epstein-Barr virus (EBV) and are defined as EBV-associated gastric carcinomas (EBVaGCs). EBVaGCs are known to be accompanied by massive CD8(+) cytotoxic T cell (CTL) infiltration; however, adoptive cellular immunotherapy based on EBV-specific CD8(+) CTLs has been explored with limited success. Because regulatory T cells (Tregs) are regarded as a critical hurdle in anti-tumour immunity, we assessed the distribution of Tregs in 45 cases of EBVaGC and 45 cases of EBV-negative gastric carcinoma (EBVnGC) with matched clinicopathological parameters by immunohistochemistry. We showed that Tregs were significantly increased in EBVaGC compared to EBVnGC (15.92 ± 11.45/HPF vs. 8.45 ± 6.16/HPF, p = 0.001). In addition, we explored the accumulation mechanisms of Tregs in EBVaGC by using EBV (+) gastric carcinoma cell lines SNU719 and GT39 as ex vivo models. When peripheral blood mononuclear cells (PBMCs) were co-cultured with EBV (+) gastric carcinoma cell lines, the Treg frequency increased, and they underwent phenotypic and functional changes. The enhanced recruitment by CCL22 produced by EBVaGC cells, the decreased emigration due to CCR7 downregulation on the Treg surface, the higher proliferation rate, and the lower apoptosis rate of Tregs at tumour sites may promote the accumulation of Tregs in EBVaGC.
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Na-na
authors.initials: NN
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Jian-ning
authors.initials: JN
authors.lastname: Chen
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Tang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Yi-wang
authors.initials: YW
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Zhi-ying
authors.initials: ZY
authors.lastname: Feng
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
authors.forename: Chun-kui
authors.initials: CK
authors.lastname: Shao
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D054422:Chemokine CCL22 / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D054400:Receptors, CCR7 / Q000276:immunology / Q000378:metabolism; D013274:Stomach Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: C515370:CCR7 protein, human; D054422:Chemokine CCL22; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D054400:Receptors, CCR7