Poor clinical outcomes of intratumoral dendritic cellespecific intercellular adhesion molecule 3-grabbing non-integrinepositive macrophages associated with immune evasion in gastric cancer
Poor clinical outcomes of intratumoral dendritic cellespecific intercellular adhesion molecule 3-grabbing non-integrinepositive macrophages associated with immune evasion in gastric cancer
复制标题
肿瘤内树突状细胞特异性细胞间粘附分子3-抓取非整合阳性巨噬细胞与胃癌免疫逃避相关的不良临床结果
DOI：
10.1016/j.ejca.2020.01.002
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发表时间：
2020-03-01
影响因子：
8.4
通讯作者：
Xu, Jiejie
中科院分区：
文献类型：
--
作者：
Liu, Xin;Cao, Yifan;Xu, Jiejie
Aim: Tumour-associated macrophages (TAMs) are prominent immune cells infiltrating in solid tumours with phenotypic and functional heterogeneity. However, the clinical significance of heterogeneous subtypes of TAMs in gastric cancer still remains obscure. Here, we aimed to explore the clinical significance of TAMs expressing dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and its relevance with immune contexture in gastric cancer.Methods: We selected 453 formalin-fixed and paraffin-embedded samples and 51 fresh tissue specimens of patients with gastric cancer from Zhongshan Hospital. The association of DC-IGN(+) macrophages with clinicopathological parameters, overall survival (OS) and responsiveness to fluorouracil-based adjuvant chemotherapy (ACT) was inspected. Immunohistochemistry (IHC) and flow cytometry (FCM) were applied to characterize immune cells in gastric cancer.Results: We demonstrated that high intratumoral DC-SIGN(+) macrophages infiltration predicted poor OS and inferior therapeutic responsiveness to fluorouracil-based ACT in patients with gastric cancer. Furthermore, higher infiltration of DC-SIGN(+) macrophages indicated an increased number of Foxp3(+) regulatory T cells (Tregs), CD8(+) T cells and a higher ratio of Foxp3(+) /CD8(+) within the tumour microenvironment (TME). In addition, CD8(+) T cells in DC-SIGN(+) macrophages high subgroup were functionally impaired, showing decreased interferon-gamma (IFN-gamma), granzyme B (GZMB) and perforin production yet elevated programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression.Conclusions: DC-SIGN(+) macrophages were associated with immunoinvasive TME and indicated poor prognosis and inferior therapeutic responsiveness to fluorouracil-based ACT. DC-SIGN(+) macrophages might be an independent prognosticator and a potential immunotherapeutic target for gastric cancer. (C) 2020 Elsevier Ltd. All rights reserved.
