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Distinct changes of dendritic cell number and IL-12 mRNA level in adjacent mucosa throughout the colorectal adenoma–carcinoma sequence

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Abstract

Adjacent mucosa may reflect the conflicting of host factors in response to the establishment or invasion of cancers. Characterization of anti-tumor immunity in this region may add help in understanding the immune-related mechanisms of colorectal carcinoma (CRC). In this study, adjacent non-tumor mucosa from 36 patients with colorectal adenoma (CRA), 26 with CRC and normal mucosa from 15 health controls were included, immune cell populations of dendritic cell, lymphocyte and macrophage were characterized with immunohistochemistry (IHC) and tissue messenger RNA (mRNA) levels of Th1 cytokines interferon (IFN)-gamma and its upstream inducers interleukin (IL)-12 and IL-18 were quantified with real-time PCR; In addition, dendritic cell differentiation and function inhibitors cyclooxygenase-2 (COX-2) and IL-6 mRNA levels were also quantified. By IHC, a significant decreased dendritic cell density in the non-tumor mucosa adjacent to CRC was detected (P < 0.05) as compared to the normal controls or adjacent mucosa of CRA. The grading scores for lymphocyte number in the adjacent mucosa of CRA and CRC were gradually non-statistically increased, while the grading scores for macrophages number was not changed. By quantitative real-time PCR, distinct local cytokine gene expression profile was demonstrated. In which, the Th1 cytokines, particularly IL-12, were increased in adjacent mucosa of CRA, but all significantly decreased in adjacent mucosa of CRC. In addition, the mRNA levels of IL-6 and COX-2 were significantly higher in adjacent mucosa of CRC than that in adjacent mucosa of CRA (both P < 0.05). Therefore, dendritic cell functional changes could be one of the important mechanisms for altered anti-tumour immunity in the adjacent non-tumor mucosa throughout adenoma–carcinoma sequence. The increased COX-2 and IL-6 might contribute to dendritic cell funtional defect in adjacent mucosa of CRC.

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Abbreviations

IFN-gamma:

Interferon gamma

IL:

Interleukin

real-time PCR:

Real-time polymerase chain reaction

RT-PCR:

Reverse-transcription polymerase chain reaction

IHC:

Immunohistochemistry

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Acknowledgments

This work was financially supported by grant from Medical Research Program, Northern Norway Regional Health Authority to Cui G (SFP-44-04). We express our sincere gratitude to our colleagues at Departments of Gastroenterology and Gastrointestinal Surgery for supplying biopsies, and to Ingrid Christiansen, Marian Remijn and Line Wilsgaard for their technical assistance.

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Authors and Affiliations

  1. Laboratory of Gastroenterology, Institute of Clinical Medicine, Faculty of Medicine, University of Tromsø, Tromsø, 9037, Norway

    Guanglin Cui, Aping Yuan, Rasmus Goll, Trine Olsen & Jon Florholmen

  2. Department of Gastroenterology, University Hospital of North Norway, Tromsø, Norway

    Guanglin Cui, Aping Yuan, Rasmus Goll, Trine Olsen & Jon Florholmen

  3. Department of Immunology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Tromsø, Norway

    Anne Husebekk

  4. Division of Gastrointestinal Surgery, University Hospital of North Norway, Tromsø, Norway

    Barthold Vonen

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  1. Guanglin Cui
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  2. Aping Yuan
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Correspondence to Guanglin Cui.

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Cui, G., Yuan, A., Goll, R. et al. Distinct changes of dendritic cell number and IL-12 mRNA level in adjacent mucosa throughout the colorectal adenoma–carcinoma sequence. Cancer Immunol Immunother 56, 1993–2001 (2007). https://doi.org/10.1007/s00262-007-0345-9

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  • DOI: https://doi.org/10.1007/s00262-007-0345-9

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