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Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma

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Abstract

B7-H3, a member of the B7-family molecules, plays an important role in adaptive immune responses, and was shown to either promote or inhibit T-cell responses in various experimental systems. B7-H3 was expressed in some human cancers and correlated with poor outcome of cancer patients. However, its exact role in cancer is not known. In the present study, we studied the expression of B7-H3 in the pathologic specimens of 102 patients treated for colorectal carcinoma (CRC) by immunohistochemistry. Strong B7-H3 expression was found in cancer tissues from 54.3% CRC patients, while minimal expression was found in adjacent normal colorectal tissues. Higher B7-H3 expression in tumor positively correlated with a more advanced tumor grade. In addition, consistent with a role of B7-H3 in suppressing tumor immune surveillance, the expression of B7-H3 in cancer cells negatively correlated with the intensity of tumor infiltrating T lymphocytes in both tumor nest and tumor stroma. Furthermore, we found that the level of soluble B7-H3 in sera from CRC patients was higher than healthy donors. TNF-α, an important cancer-promoting inflammatory molecule, was subsequently found to significantly increase the release of soluble B7-H3 in colon cancer cell lines. Therefore, our data suggest that both soluble and membranous B7-H3 proteins are involved in colon cancer progression and evasion of cancer immune surveillance.

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Acknowledgments

We thank senior pathologists Chang-qing Lu, Min Tan, Yuan-dong Chen and Prof. Tong-yu Chen (Department of Pathology, The Third Affiliated Hospital of Suzhou University, Jiangsu Changzhou 213003, China) for their excellent expert suggestions and technical assistances. We also thank Dr. Jeff Kovacs and Ms. Christen Shiber (Department of Immunology, University of Pittsburgh) for editing the manuscript. This work was supported by grants from the Major State Basic Research Development Program of China (973 Program: CB51003), the National Natural Science Foundation of China (No. 30801023 and No. 30930085), and the advanced program of Commission of Technology and Industry for National Defense (A3820060130).

Conflict of interest statement

The authors declare that they have no competing interests to this paper.

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Authors and Affiliations

  1. Institute of Medical Biotechnology, Medical College of Suzhou University, 708 Renmin Road, Suzhou, 215007, Jiangsu, China

    Jing Sun, Lu-jun Chen, Ming Zhu & Xue-guang Zhang

  2. Clinical Immunology Laboratory, The First Affiliated Hospital of Suzhou University, Suzhou, 215007, Jiangsu, China

    Guang-bo Zhang

  3. Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University, Changzhou, 213003, Jiangsu, China

    Jing-ting Jiang

  4. Department of Pathology, The Third Affiliated Hospital, Suzhou University, Changzhou, 213003, Jiangsu, China

    Yan Tan

  5. Department of Gastrointestinal Surgery, The Third Affiliated Hospital, Suzhou University, Changzhou, 213003, Jiangsu, China

    Hai-tao Wang

  6. Department of Immunology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Bin-feng Lu

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  1. Jing Sun
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  2. Lu-jun Chen
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  3. Guang-bo Zhang
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  6. Yan Tan
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Correspondence to Xue-guang Zhang.

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J. Sun and L. Chen contributed equally to this work.

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Sun, J., Chen, Lj., Zhang, Gb. et al. Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma. Cancer Immunol Immunother 59, 1163–1171 (2010). https://doi.org/10.1007/s00262-010-0841-1

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