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Functional Down-Regulation of β1 and β2 Integrins on Lamina Propria Lymphocytes (LPL) and Tumor-Infiltrating Lymphocytes (TIL) in Colorectal Cancer Patients

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Abstract

Integrins play an important role in various lymphocyte functions. In this study, we isolated lamina propria lymphocytes (LPL) and tumor-infiltrating lymphocytes (TIL) from normal and malignant tissues in patients with colorectal cancer, and examined the expression of β1 and β2 integrins on these lymphocytes quantitatively with two-color flow cytometry. Both LPL and TIL expressed a lower level of common β1 chain (CD29) in CD4 and CD8 subpopulations than did peripheral blood lymphocytes (PBL). Among the associated α chains, the expression levels of α1 (CD49a) and α2 (CD49b) were slightly higher, whereas those of α4 (CD49d) and α6 (CD49f) were markedly reduced in LPL and TIL. No significant differences were observed in expressions of any β1 integrin chains between these two lymphocytes populations. Similarly, both αL (CD11a) and β2 (CD18) were down-regulated in TIL and LPL with CD8+ cytotoxic phenotype, but not in those with CD4+ phenotype. CD8+ TIL expressed a slightly but significantly higher level of αLβ2 than did CD8+ LPL. CD8+ LPL and CD8+ TIL consistently showed significantly decreased binding to purified ICAM-1, VCAM-1 and HT29 colon cancer cells as compared with CD8+ PBL. Although CD8+ TIL showed a slightly higher level of adhesion to these substrates than did CD8+ LPL, the level was much lower than that in PBL. The expression pattern and functional down-regulation of these integrins may be one of the reasons why TIL cannot eradicate the cancer cells in colorectal cancer.

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Authors and Affiliations

  1. Department of Surgery, Division of Surgical Oncology (The First Department of Surgery), The University of Tokyo, Hongo 7–3-1, Bunkyo-ku, Tokyo, 113, Japan

    Hiroshi Nakayama MD, Tetsuichiro Muto MD & Hirokazu Nagawa MD

  2. Department of Transfusion Medicine, The University of Tokyo, Tokyo, Japan

    Nelson Tuno MD & Yoichi Shibata MD

  3. Department of Surgery, Division of Surgical Oncology (The First Department of Surgery), The University of Tokyo, Hongo 7–3-1, Bunkyo-ku, Tokyo, 113, Japan

    Joji Kitayama MD

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  1. Joji Kitayama MD
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  2. Nelson Tuno MD
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  3. Hiroshi Nakayama MD
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  4. Yoichi Shibata MD
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  5. Tetsuichiro Muto MD
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  6. Hirokazu Nagawa MD
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Kitayama, J., Tuno, N., Nakayama, H. et al. Functional Down-Regulation of β1 and β2 Integrins on Lamina Propria Lymphocytes (LPL) and Tumor-Infiltrating Lymphocytes (TIL) in Colorectal Cancer Patients. Ann Surg Oncol 6, 500–506 (1999). https://doi.org/10.1007/s10434-999-0500-y

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  • DOI: https://doi.org/10.1007/s10434-999-0500-y

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