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Differentiated tumor immune microenvironment of Epstein-Barr virus-associated and negative gastric cancer: implication in prognosis and immunotherapy

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机构: [1]Fourth Mil Med Univ, State Key Lab Canc Biol, Xian, Shaanxi, Peoples R China; [2]Fourth Mil Med Univ, Inst Digest Dis, Xijing Hosp, Xian, Shaanxi, Peoples R China; [3]Fourth Mil Med Univ, Tangdu Hosp, Dept Infect Dis, Xian, Shaanxi, Peoples R China; [4]Fourth Mil Med Univ, Pathol Dept, Xian, Shaanxi, Peoples R China; [5]Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, State Key Lab Digest Dis, Inst Digest Dis, Shenzhen, Guangdong, Peoples R China; [6]Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, State Key Lab Digest Dis, Dept Med & Therapeut, Shenzhen, Guangdong, Peoples R China; [7]Chinese Univ Hong Kong, Shenzhen Res Inst, Shenzhen, Guangdong, Peoples R China; [8]Sun Yat Sen Univ, Canc Ctr, Dept Expt Res, Collaborat Innovat Ctr Canc Med,State Key Lab Onc, Guangzhou, Guangdong, Peoples R China
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关键词: gastric cancer tumor microenvironment Epstein-Barr virus tumor-infiltrating lymphocytes immune checkpoint

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Epstein-Barr virus-associated gastric cancer (EBVaGC) has been proposed to be a distinct subtype with a specific immune microenvironment. Here, we evaluated tumor-infiltrating T-cell subsets and the expression of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) in 571 gastric cancers (GCs). Tissue microarrays were stained using EBER in situ hybridization for EBV and using immunohistochemistry for CD4, CD8, Foxp3, PD-1 and PD-L1. GCs were categorized into four types based on CD8(+) infiltration and PD-L1 expression. The 5-year overall survival (OS) was evaluated according to EBV infection, T-cell subsets, PD-1 and PD-L1 expression and immune types. Thirty-two (5.3%) EBVaGCs were identified, which were more prevalent for CD8(+) (p<0.001) and Foxp3(+) (p=0.020) cell infiltration than EBV-negative GCs (EBVnGCs), suggesting a better 5-year OS (p=0.003). CD8(+) (p=0.001) and Foxp3(+) (p=0.018) cell infiltration was associated with better 5-year OS, whereas PD-L1 expression correlated with a poor 5-year OS (p=0.002). EBVaGC and EBVnGC had heterogeneous immune microenvironment, with CD8(+) PD-L1-GC exhibiting the best 5-year OS (p<0.001). GC was an immune ignorant dominant tumor and poor to no T-cell infiltration. An immune type classification algorithm can provide prognostic information and a rational basis for immunotherapy.

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出版当年[2017]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学 3 区 细胞生物学
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第一作者机构: [1]Fourth Mil Med Univ, State Key Lab Canc Biol, Xian, Shaanxi, Peoples R China; [2]Fourth Mil Med Univ, Inst Digest Dis, Xijing Hosp, Xian, Shaanxi, Peoples R China;
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通讯机构: [1]Fourth Mil Med Univ, State Key Lab Canc Biol, Xian, Shaanxi, Peoples R China; [2]Fourth Mil Med Univ, Inst Digest Dis, Xijing Hosp, Xian, Shaanxi, Peoples R China;
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