caa a22 4500 445330988 CHVBK 20180317142737.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s10689-011-9449-7 doi (NATIONALLICENCE)springer-10.1007/s10689-011-9449-7 Dendritic cell and macrophage infiltration in microsatellite-unstable and microsatellite-stable colorectal cancer [Elektronische Daten] [Kathrin Bauer, Sara Michel, Miriam Reuschenbach, Nina Nelius, Magnus von Knebel Doeberitz, Matthias Kloor] High level microsatellite instability (MSI-H) is a hallmark of Lynch syndrome-associated colorectal cancer (CRC). MSI-H CRC express immunogenic tumour antigens as a consequence of DNA mismatch repair deficiency-induced frameshift mutations. Consequently, frameshift antigen-specific immune responses are commonly observed in patients with Lynch syndrome-associated MSI-H CRC. Dendritic cells (DC) and macrophages play a crucial role in the induction and modulation of immune responses. We here analysed DC and macrophage infiltration in MSI-H and microsatellite-stable CRC. Sixty-nine CRC (MSI-H, n=33; microsatellite-stable, n=36) were examined for the density of tumour-infiltrating DC, Foxp3-positive regulatory T cells, and CD163-positive macrophages. In MSI-H lesions, S100-positive and CD163-positive cell counts were significantly higher compared to microsatellite-stable lesions (S100: epithelium P=0.018, stroma P=0.042; CD163: epithelium P<0.001, stroma P=0.046). Additionally, numbers of CD208-positive mature DC were significantly elevated in the epithelial compartment of MSI-H CRC (P=0.027). High numbers of tumour-infiltrating Foxp3-positive T cells were detected in tumours showing a low proportion of CD208-positive, mature DC among the total number of S100-positive cells. Our study demonstrates that infiltration with DC, mature DC, and macrophages is elevated in MSI-H compared to microsatellite-stable CRC. The positive correlation of Foxp3-positive Treg cell density with a low proportion of mature DC suggests that impaired DC maturation may contribute to local immune evasion in CRC. Our results demonstrate that DC and macrophages in the tumour environment likely play an important role in the induction of antigen-specific immune responses in Lynch syndrome. Moreover, impaired DC maturation might contribute to local immune evasion in CRC. Springer Science+Business Media B.V., 2011 Colorectal cancer nationallicence Dendritic cells nationallicence Immune response nationallicence Lynch syndrome nationallicence Macrophages nationallicence Microsatellite instability nationallicence Regulatory T cells nationallicence CRC : Colorectal cancer nationallicence DC : Dendritic cells nationallicence MSI-H : High-level microsatellite instability nationallicence MSS : Microsatellite-stable nationallicence Treg cells : Regulatory T cells nationallicence Bauer Kathrin Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut Michel Sara Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut Reuschenbach Miriam Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut Nelius Nina Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut von Knebel Doeberitz Magnus Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut Kloor Matthias Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut Familial Cancer Springer Netherlands 10/3(2011-09-01), 557-565 1389-9600 10:3<557 2011 10 10689 https://doi.org/10.1007/s10689-011-9449-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-011-9449-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bauer Kathrin Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut NATIONALLICENCE 700 1- Michel Sara Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut NATIONALLICENCE 700 1- Reuschenbach Miriam Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut NATIONALLICENCE 700 1- Nelius Nina Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut NATIONALLICENCE 700 1- von Knebel Doeberitz Magnus Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut NATIONALLICENCE 700 1- Kloor Matthias Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/3(2011-09-01), 557-565 1389-9600 10:3<557 2011 10 10689 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer