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Reduced expression of microenvironmental Th1 cytokines accompanies adenomas–carcinomas sequence of colorectum

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Abstract

Cytokines have been suggested to be key factors in modulating immune response against tumorigenesis in the microenvironment. Therefore, characterization of cytokine expression along the colorectal adenoma–carcinoma sequence may add important information for understanding the immune-related mechanisms of the development of colorectal carcinoma (CRC). In this study, biopsies from 32 patients with colorectal adenoma (CRA), 20 patients with CRC and 18 healthy controls were examined. Cytokine gene expressions of interleukin-4 (IL-4), IL-10, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and its upstream inducers (IL-12A and IL-18) were measured at messenger RNA (mRNA) level with quantitative real-time PCR (Q-PCR). Cytokine expressing cells were characterized using immunohistochemistry (IHC). A distinct different cytokine profile between adenoma and CRC was observed: the Th1 cytokines (IFN-gamma, TNF-alpha, IL-12A and IL-18) were increased in local tissues of CRA and decreased in CRC. Consistent with the quantitative cytokine data, IHC examinations revealed slightly increased densities of Th1 cytokine-expressing cells in CRA and a remarkably decreased density of the Th1 cells in CRC. In CRA, the cytokine-expressing cells were highly polarized to the subepithelial stroma while the cells were evenly distributed through the stroma in CRC. In conclusion, distinct changes in the Th1 cytokine profile appear along the colorectal adenoma–carcinoma sequence. This may reflect a change in the host immune regulatory function in the adenoma–carcinoma sequence.

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Abbreviations

TNF alpha :

Tumor necrosis factor alpha

IFN:

Gamma Interferon gamma

IL:

Interleukin

Q-PCR:

Quantitative real-time polymerase chain reaction

IHC:

Immunohistochemistry

CRA:

Colorectal adenoma

CRC:

Colorectal carcinoma

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Acknowledgments

This work was financially supported by grant from Helse Nord to Cui G (SFP-44-05). We express our sincere gratitude to our colleagues at Dept. of Gastroenterology and Dept. of Gastrointestinal Surgery for supplying biopsies; and to Mss, Ingrid Christiansen, Marian Remijn and Line Wilsgaard for technical assistance.

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Authors and Affiliations

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

    Guanglin Cui, Rasmus Goll, Trine Olsen & Jon Florholmen

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

    Sonja Eriksson Steigen

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

    Anne Husebekk

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

    Barthold Vonen

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  1. Guanglin Cui
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Correspondence to Guanglin Cui.

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Cui, G., Goll, R., Olsen, T. et al. Reduced expression of microenvironmental Th1 cytokines accompanies adenomas–carcinomas sequence of colorectum. Cancer Immunol Immunother 56, 985–995 (2007). https://doi.org/10.1007/s00262-006-0259-y

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  • DOI: https://doi.org/10.1007/s00262-006-0259-y

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