Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells.
Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells.
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DOI：
10.4049/jimmunol.1101304
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发表时间：
2012-02-15
期刊：
影响因子：
--
通讯作者：
Klinman DM
中科院分区：
文献类型：
--
作者：
Shirota Y;Shirota H;Klinman DM
免疫刺激CpG寡核苷酸（ODN）激活表达tlr9的细胞，并已被证明可以改善宿主对肿瘤抗原的反应。不幸的是，许多癌症周围的免疫抑制微环境会抑制ag特异性细胞反应，从而干扰cpg介导的免疫治疗。髓源性抑制细胞（MDSC）是这种免疫抑制环境的重要组成部分。大量的MDSC存在于肿瘤部位及其附近，它们抑制抗原特异性T细胞和NK细胞的活性。目前的研究表明，CpG ODN直接递送到肿瘤床降低了单核细胞（CD11b+, Ly6G−,ly6high） MDSC的免疫抑制活性。单核细胞MDSC表达TLR9，对CpG刺激的反应是：1)失去抑制T细胞功能的能力，2)产生Th1细胞因子，3)分化为具有杀瘤能力的巨噬细胞。这些发现为CpG ODN促进肿瘤消退的新机制提供了见解，并支持肿瘤内注射作为其递送的最佳途径。
Immunostimulatory CpG oligonucleotides (ODN) activate cells that express TLR 9 and have been shown to improve the host’s response to tumor antigens. Unfortunately, the immunosuppressive microenvironment that surrounds many cancers inhibits Ag-specific cellular responses and thus interferes with CpG-mediated immunotherapy. Myeloid-derived suppressor cells (MDSC) represent an important constituent of this immunosuppressive milieu. Large numbers of MDSC are present in and near tumor sites where they inhibit the activity of antigen-specific T and NK cells. Current studies indicate that the delivery of CpG ODN directly into the tumor bed reduces the immunosuppressive activity of monocytic (CD11b+, Ly6G−, Ly6Chigh) MDSC. Monocytic MDSC express TLR9 and respond to CpG stimulation by i) losing their ability to suppress T cell function, ii) producing Th1 cytokines and iii) differentiating into macrophages with tumoricidal capability. These findings provide insight into a novel mechanism by which CpG ODN contribute to tumor regression, and support intra-tumoral injection as the optimal route for their delivery.
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癌症扩增的骨髓源性抑制细胞通过膜结合 TGF-β1 诱导 NK 细胞无反应。
影响因子：
4.4
作者：
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DOI：
10.1007/s00262-011-0973-y
发表时间：
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期刊：
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影响因子：
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作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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