Tumor-infiltrating macrophages and dendritic cells in human colorectal cancer: relation to local regulatory T cells, systemic T-cell response against tumor-associated antigens and survival
Tumor-infiltrating macrophages and dendritic cells in human colorectal cancer: relation to local regulatory T cells, systemic T-cell response against tumor-associated antigens and survival
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DOI：
10.1186/1479-5876-5-62
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发表时间：
2007-11-29
影响因子：
7.4
通讯作者：
Loddenkemper, Christoph
中科院分区：
文献类型：
--
作者：
Nagorsen, Dirk;Voigt, Sabine;Loddenkemper, Christoph
简介：尽管已经在结直肠癌 (CRC) 中研究了针对肿瘤抗原的全身 T 细胞反应和 T 细胞的肿瘤浸润，但原位自发免疫反应的启动尚不清楚。巨噬细胞和树突状细胞 (DC) 作为先天免疫反应和适应性免疫反应之间的纽带发挥着重要作用。本研究的目的是分析 CRC 中的巨噬细胞和 DC 浸润，并调查其与全身 T 细胞反应、调节性 T 细胞 (Treg) 浸润和存活是否存在相关性。方法：使用 40 例结直肠癌中的 9 种巨噬细胞和 DC 标记物（CD68、CD163、S100、CD11c、CD208、CD209、CD123、CD1a、Langerin）进行免疫组织学染色结果：所有标本均在上皮肿瘤组织和肿瘤基质中含有 CD68、CD163、S100 和 CD1a 阳性细胞。样本中仅检测到极少数（少于中位数 3/HPF）CD123+、CD1a+、CD11c+、CD 208+、CD209+ 或 Langerin+ 细胞。总体而言，我们发现在没有 T 细胞反应的患者中，S100 阳性 DC 的浸润有增加的趋势，并且基质 S100 阳性 DC 的数量显着增加。有限疾病中基质 S100 DC 和 CD163 巨噬细胞增加（S100：11.1/HPF 与 7.3/HPF，p = 0.046；CD163：11.0/HPF 与 8.1/HPF，p = 0.06）。我们发现 S100 阳性 DC 和 FOXP3 阳性 Tregs 之间存在显着的正相关性。高 DC 浸润患者的生存率明显好于低 DC 浸润患者（p < 0.05）。此外，我们发现 CD163 阳性巨噬细胞浸润增加导致生存率提高的趋势 (p = 0.07)。结论：目前的原位研究为先天性免疫系统和过继性免疫系统之间相互作用的讨论添加了新数据。我们的数据强烈支持这样的假设：肿瘤浸润 DC 是恶性疾病中先天性免疫反应和适应性免疫反应之间的关键因素。肿瘤浸润性 S100 阳性 DC 与全身抗原特异性 T 细胞反应呈负相关，与调节性 T 细胞呈正相关，与 CRC 生存呈正相关。这些数据将肿瘤浸润 DC 置于 CRC 相关免疫反应的中心。
Introduction: Although systemic T-cell responses against tumor antigens and tumor infiltration by T cells have been investigated in colorectal cancer (CRC), the initiation of spontaneous immune responses in situ is not well understood. Macrophages and dendritic cells (DC) play an important role as a link between innate and adaptive immune response. The aim of the present study was to analyze macrophage and DC infiltration in CRC and to investigate whether there is a correlation to systemic T-cell response, regulatory T cell (Treg) infiltration, and survival.Methods: Immunohistological staining was performed with nine markers for macrophages and DC (CD68, CD163, S100, CD11c, CD208, CD209, CD123, CD1a, Langerin) in 40 colorectal cancer samples from patients, in whom the state of systemic T-cell responses against tumor-associated antigens (TAA) and Treg infiltration had previously been determined.Results: All specimens contained cells positive for CD68, CD163, S100 and CD1a in epithelial tumor tissue and tumor stroma. Only a very few (less than median 3/HPF) CD123+, CD1a+, CD11c+, CD 208+, CD209+, or Langerin+ cells were detected in the specimens. Overall, we found a trend towards increased infiltration by S100-positive DC and a significantly increased number of stromal S100-positive DC in patients without T-cell response. There was an increase of stromal S100 DC and CD163 macrophages in limited disease (S100: 11.1/HPF vs. 7.3/HPF, p = 0.046; CD163: 11.0/HPF vs. 8.1/HPF, p = 0.06). We found a significant, positive correlation between S100-positive DC and FOXP3-positive Tregs. Survival in patients with high DC infiltration was significantly better than that in those with low DC infiltration (p < 0.05). Furthermore, we found a trend towards better survival for increased infiltration with CD163-positive macrophages (p = 0.07).Conclusion: The present in situ study adds new data to the discussion on the interaction between the innate and adoptive immune system. Our data strongly support the hypothesis that tumor-infiltrating DC are a key factor at the interface between innate and adaptive immune response in malignant disease. Tumor infiltrating S100-positive DC show an inverse relationship with the systemic antigen-specific T-cell response, a positive correlation with regulatory T cells, and a positive association with survival in CRC. These data put tumor-infiltrating DC at the center of the relevant immune response in CRC.