Non-small Cell Lung Cancer Induces an Immunosuppressive Phenotype of Dendritic Cells in Tumor Microenvironment by Upregulating B7-H3
Non-small Cell Lung Cancer Induces an Immunosuppressive Phenotype of Dendritic Cells in Tumor Microenvironment by Upregulating B7-H3
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DOI：
10.1097/jto.0b013e31821c421d
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发表时间：
2011-07-01
影响因子：
20.4
通讯作者：
Mahnke, Karsten
中科院分区：
文献类型：
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作者：
Schneider, Thomas;Hoffmann, Hans;Mahnke, Karsten
简介：肿瘤可能会将树突状细胞 (DC) 的表型和功能转变为诱导耐受。在完全成熟的状态下，DC表达大量T细胞共刺激分子，使它们能够诱导免疫反应，而未激活的常驻DC缺乏这些T细胞刺激能力。因此，我们研究了非小细胞肺癌（NSCLC）诱导的DC表型和B7-H分子表达的变化。方法：分析了从接受NSCLC根治性手术的患者（n = 12）的恶性和非恶性肺和淋巴结组织中分离的DC上T细胞共抑制B7分子（B7-DC、B7-1、B7-2、B7-H1、B7-H3）的表达。通过同种异体混合淋巴细胞反应测量从恶性和非恶性肺和淋巴结组织样本中分离的DC的T细胞刺激功能。此外，还分析了 DC 分泌 IL-10 和 IL-12p40 的情况（酶联免疫吸附测定）。结果：B7-H3 在肿瘤驻留 DC 中显着上调，而其他 B7 分子（如 B7-DC、B7-1、B7-2、B7-H1）的表达保持不变。记录到与肿瘤源性 DC 混合的淋巴细胞反应中 T 细胞增殖水平显着降低。此外，在肿瘤来源的 DC 中检测到 IL-10 浓度升高，而 IL-12 水平降低。结论：我们的数据表明，(1) NSCLC 来源的 DC 具有免疫抑制作用，(2) 在肿瘤条件下，共抑制分子 B7-H3 在介导 DC 的 T 细胞抑制作用中发挥着至关重要的作用。
Introduction: Tumors may shift the phenotype and function of dendritic cells (DC) toward the induction of tolerance. In the status of full maturity, DC express a multitude of T cell costimulatory molecules enabling them to induce immune reactions, whereas nonactivated resident DC lack these T cell stimulating capacities. Therefore, we investigated the changes in DC phenotype and expression of B7-H molecules induced by non-small cell lung cancer (NSCLC).Methods: The expression of T cell coinhibitory B7 molecules (B7-DC, B7-1, B7-2, B7-H1, B7-H3) on DC isolated from malignant and nonmalignant lung and lymph node tissue from patients attending curative surgery for NSCLC (n = 12) was analyzed. T cell stimulatory functions of DC isolated from malignant and nonmalignant lung and lymph node tissue samples were measured by allogeneic mixed lymphocyte reactions. Furthermore, the secretion of IL-10 and IL-12p40 by DC was analyzed (enzyme-linked immunosorbent assay).Results: B7-H3 was significantly upregulated in tumor-residing DC, whereas the expression of other B7 molecules, such as B7-DC, B7-1, B7-2, B7-H1, remained unchanged. Significantly reduced levels of T cell proliferation in mixed lymphocyte reactions with tumor-derived DC were recorded. Moreover, elevated concentrations of IL-10 were measured in tumor-derived DC, whereas IL-12 levels were reduced.Conclusion: Our data indicate that (1) DC derived from NSCLC are immunosuppressive, and (2) under tumor conditions the coinhibitory molecule B7-H3 plays a crucial role in mediating the T cell suppressive effects of DC.