A novel role of metalloproteinase in cancer-mediated immunosuppression

Bor Ching Sheu, Su Ming Hsu, Hong Nerng Ho, Huang Chun Lien, Su Cheng Huang, Rong Hwa Lin

Research output: Contribution to journalArticle

236 Citations (Scopus)

Abstract

Depressed immune responses have been observed frequently in cancer patients. In a variety of human malignancies, the expression of interleukin-2 receptor α (IL-2Rα) on activated tumor-infiltrating lymphocytes was down-regulated. Because IL-2Rα plays a pivotal role in the development and propagation of functional T cells, its depressed expression may result in poor function of tumor-reactive cytotoxic lymphocytes. For elucidating the mechanism responsible for down-regulation of IL-2Rα, a coculture model of in vitro mixed autologous lymphocytes and tumor cells was established. Kinetic analysis showed that cervical cancer cells downregulated IL-2Rα expression on encountered T cells. The amount of IL-2Rα mRNA in tumor-infiltrating lymphocytes-derived CD8 + T cells was compatible with that in the corresponding activated CD8 + T cells. Additional evidence showed that cervical cancer cells could induce the release of soluble IL-2Rα expression on encountered T cells. By using protease inhibition assays we demonstrated that tissue inhibitors of metalloproteinase abrogated the cancer-mediated IL-2Rα proteolytic process and restored the T-cell proliferation function. Immunohistochemical stainings further revealed prominent metalloproteinase (MMP) expressions, including MMP-1, MMP-2, and MMP-9, in cervical cancer tissues. Additional in vitro studies showed that MMP-9 mediates cleavage of IL-2Rα and down-regulates the proliferative capability of cancer-encountered T cells. Our findings suggest a new role of MMPs in tumor-mediated immunosuppression and provide a possible therapeutic potential for patients with cervical cancer.

Original languageEnglish
Pages (from-to)237-242
Number of pages6
JournalCancer Research
Volume61
Issue number1
Publication statusPublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'A novel role of metalloproteinase in cancer-mediated immunosuppression'. Together they form a unique fingerprint.

  • Cite this

    Sheu, B. C., Hsu, S. M., Ho, H. N., Lien, H. C., Huang, S. C., & Lin, R. H. (2001). A novel role of metalloproteinase in cancer-mediated immunosuppression. Cancer Research, 61(1), 237-242.