CCR9-CCL25 mediated plasmacytoid dendritic cell homing and contributed the immunosuppressive microenvironment in gastric cancer.
CCR9-CCL25 mediated plasmacytoid dendritic cell homing and contributed the immunosuppressive microenvironment in gastric cancer.
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DOI：
10.1016/j.tranon.2023.101682
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发表时间：
2023-07
影响因子：
5
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Yu H;Mei Y;Dong Y;Chen C;Lin X;Jin H;Yu J;Liu X
趋化因子受体9和趋化因子配体25相互作用介导的胃癌免疫抑制微环境在组织和外周血中分别检测到浆细胞样树突状细胞（pDCs）和调节性t细胞（Tregs）。CCL-25在癌组织中过表达。CCR9+pDCs和ICOS+ tregs在癌组织和外周血中显著升高。在晚期t分期患者和淋巴结转移患者中发现更多CCR9+ pDCs，预后较差。CCR9-CCL25相互作用可能在介导PDC归巢到转移淋巴结和癌组织中发挥重要作用，从而导致肿瘤免疫抑制微环境和不良预后。浆细胞样树突状细胞在肿瘤微环境中起着至关重要的作用。有证据表明趋化因子受体9 （chemokine receptor 9, CCR9）是吸引pDCs归巢到消化道的重要分子，后者参与消化道免疫耐受的形成。本研究旨在探讨CCR9-CCL25相互作用在pdc介导的胃癌（GC）免疫抑制微环境中的作用。免疫组化检测调节性T细胞（Tregs）和pDCs。免疫荧光法观察在pDC上表达的CCR9。Western Blot检测CCL-25的表达。流式细胞术分析外周血和引流淋巴结总pDCs、CCR9+pDCs、CCR9−pDCs、总Tregs、诱导共刺激物+ (ICOS) Tregs和ICOS−Tregs。GC组织中总Tregs、总pDCs和CCR9+pDCs含量较高。CCL-25在癌组织中过表达。GC患者外周血总pDCs、CCR9−pDCs、总Tregs、ICOS+ Tregs、ICOS−Tregs显著升高。转移性淋巴结中总pDCs、CCR9+ pDCs、总Tregs、ICOS+ Tregs较多。GC患者血浆IL-6和IL-10浓度明显升高。在T分期较晚和淋巴结转移的患者中发现更多CCR9+ pDCs浸润癌组织，预后较差。CCR9-CCL25相互作用可能在介导PDC归巢到转移淋巴结和癌组织中发挥重要作用，从而导致肿瘤免疫抑制微环境的形成和不良预后。
Chemokine receptor 9 (CCR9) and chemokine ligand 25 (CCL-25) interaction mediated immunosuppression microenvironment of gastric cancer. Plasmacytoid dendritic cells (pDCs) and regulatory t cells (Tregs) were detected in tissue and peripheral blood, respectively. CCL-25 was over-expressed in carcinoma tissue. CCR9+pDCs and ICOS+ tregs were significantly increased in carcinoma tissue and peripheral blood. More CCR9+ pDCs were found in later t staging patients and lymph node metastasis and conferred poor prognosis. CCR9-CCL25 interaction might play an important role in mediating PDC homing to metastatic lymph nodes and carcinoma tissue, which contributed to tumor immunosuppressive microenvironment and poor prognosis. Plasmacytoid dendritic cells (pDCs) play a crucial role in the microenvironment of tumor. Evidences has been shown that chemokine receptor 9 (CCR9) is an important molecule that attracts pDCs homing to the digestive tract and the latter are involved in the formation of digestive tract immune tolerance. The aim of this study was to explore the role of CCR9-CCL25 interaction in pDC-mediated immunosuppression microenvironment of gastric cancer (GC). Regulatory T cells (Tregs) and pDCs were detected by immunohistochemistry. CCR9, which expressed on pDC was visualized by immunofluorescence. Western Blot was applied to evaluate the expression of CCL-25. Total pDCs, CCR9+pDCs, CCR9−pDCs, total Tregs, inducible costimulator + (ICOS) Tregs and ICOS−Tregs in peripheral blood and draining lymph nodes were analyzed by flow cytometry. Plasma concentration of the cytokines were measured by enzyme-linked immunosorbent assay Total Tregs, pDCs and CCR9+pDCs were higher in GC tissue. CCL-25 was over-expressed in carcinoma tissue. Peripheral total pDCs, CCR9−pDCs, total Tregs, ICOS+ Tregs, ICOS− Tregs were significantly increased in GC patients. More total pDCs, CCR9+ pDCs, total Tregs, ICOS+ Tregs were found in metastatic lymph nodes. Plasma concentrations of IL-6 and IL-10 were significantly higher in GC patients. More CCR9+ pDCs were found infiltrating carcinoma tissue in patients with later T staging and lymph node metastasis and conferred a poor prognosis. CCR9-CCL25 interaction might play an important role in mediating PDC homing to metastatic lymph nodes and carcinoma tissue, which contributed to the formation of tumor immunosuppressive microenvironment and poor prognosis.
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影响因子：
2.6
作者：
Butsch, Raphael;Waelti, Stephan Lukas;Kurrer, Michael
通讯作者：
Kurrer, Michael
影响因子：
12.8
作者：
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影响因子：
11.2
作者：
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通讯作者：
Bendriss-Vermare, Nathalie
影响因子：
7.3
作者：
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