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首页> 外文期刊>Journal of Translational Medicine >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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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

机译:大肠癌中浸润肿瘤的巨噬细胞和树突状细胞:与局部调节性T细胞,针对肿瘤相关抗原的全身性T细胞应答和存活率的关系

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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 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.
机译:引言尽管在结直肠癌(CRC)中已经研究了针对肿瘤抗原的全身性T细胞应答和T细胞对肿瘤的浸润,但是对自发性原位免疫应答的启动尚不甚了解。巨噬细胞和树突状细胞(DC)在先天性和适应性免疫反应之间起着重要的作用。本研究的目的是分析CRC中的巨噬细胞和DC浸润,并调查是否与全身性T细胞反应,调节性T细胞(Treg)浸润和存活率相关。方法对来自40例大肠癌患者的巨噬细胞和DC(CD68,CD163,S100,CD11c,CD208,CD209,CD123,CD1a,Langerin)的9种标记物进行免疫组织学染色,其中系统性T细胞应答先前已经确定了肿瘤相关抗原(TAA)和Treg浸润。结果所有标本均含有上皮肿瘤组织和间质中CD68,CD163,S100和CD1a阳性的细胞。标本中仅检测到极少数(小于中值3 / HPF)CD123 +,CD1a +,CD11c +,CD 208 +,CD209 +或Langerin +细胞。总体而言,我们发现在无T细胞反应的患者中,S100阳性DC渗透增加的趋势以及基质S100阳性DC的数量显着增加。在有限疾病中基质S100 DC和CD163巨噬细胞增加(S100:11.1 / HPF对7.3 / HPF,p = 0.046; CD163:11.0 / HPF对8.1 / HPF,p = 0.06)。我们发现S100阳性DC和FOXP3阳性Treg之间存在显着的正相关。高DC浸润患者的生存率显着优于低DC浸润患者(p结论本原位研究为关于先天免疫与过继免疫系统之间相互作用的讨论增加了新数据。我们的数据有力地支持了以下假设:肿瘤浸润DC是恶性疾病先天性与适应性免疫反应之间的关键因素,肿瘤浸润S100阳性DC与全身性抗原特异性T细胞反应呈负相关,与调节性T细胞呈正相关,这些数据将肿瘤浸润DC置于CRC相关免疫反应的中心。

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