医学
渗透(HVAC)
肿瘤微环境
免疫系统
CD8型
癌症
免疫组织化学
内科学
组织微阵列
化疗
癌症研究
肿瘤科
免疫学
热力学
物理
作者
Hong-Yu Zhang,Ruochen Li,Yifan Cao,Yun Gu,Chao Lin,Xin Liu,Kunpeng Lv,Xudong He,Hanji Fang,Kaifeng Jin,Yuchao Fei,Yifan Chen,Jieti Wang,Hao Liu,He Li,Heng Zhang,Hongyong He,Weijuan Zhang
出处
期刊:Annals of Surgery
[Ovid Technologies (Wolters Kluwer)]
日期:2020-06-11
卷期号:275 (4): e626-e635
被引量:111
标识
DOI:10.1097/sla.0000000000004037
摘要
Objective: To investigate the clinical significance of IL-10 + tumor-associated macrophages (TAMs) in gastric cancer. Background: Due to the plasticity and diversity of TAMs, it is necessary to phenotypically and functionally classify subsets of TAMs to better understand the critical role of TAMs in cancer progression. TAMs expressing interleukin-10 (IL-10) have been found to facilitate immune evasion in many malignancies, but the role of IL-10 + TAMs in gastric cancer remains obscure. Methods: Four hundred and sixty-eight tumor tissue microarray specimens, 52 fresh tumor tissue samples of gastric cancer patients from Zhongshan Hospital, and data of 298 gastric cancer patients from the Cancer Genome Atlas (TCGA) were analyzed. IL-10 + TAM level and immune contexture were examined by CIBERSORT, immunohistochemistry, and flow cytometry. Clinical outcomes were analyzed by Kaplan–Meier curves and Cox model. Results: Gastric cancer patients with high IL-10 + TAM infiltration exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy. IL-10 + TAM infiltration yielded an immunoevasive tumor microenvironment featured by regulatory T cell infiltration and CD8 + T cell dysfunction. The combinational analysis of IL-10 + TAM and CD8 + T cell infiltration stratified patients into distinct risk groups with different clinical outcomes. Moreover, IL-10 + TAM infiltration was correlated with tumor-intrinsic characteristics including EBV status, PD-L1 expression, and genome stability in gastric cancer. Conclusions: This study revealed that IL-10 + TAMs might drive an immunoevasive microenvironment and determine poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy, indicating IL-10 + TAMs could be applied as a potential target for immunotherapeutic approach in gastric cancer.
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