Predominant Th2/Tc2 polarity of tumor-infiltrating lymphocytes in human cervical cancer

B. C. Sheu, R. H. Lin, Huang Chun Lien, H. N. Ho, S. M. Hsu, S. C. Huang

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Abstract

Cytotoxic T lymphocytes (Tc) play a central role in cellular immunity against cancers. The cytotoxic potential of freshly isolated tumor-infiltrating lymphiocytes (TILs) is usually not expressed. This suggests the possible existence of as yet unspecified and perhaps complex immunosuppressive factors or cytokines that affect the anti-tumor capacity of these TILs in the tumor milieu. In the present study, we demonstrated for the first time that TILs derived from human cervical cancer tissue consist mainly of Th2/Tc2 phenotypes. In vitro kinetic assays further revealed that cancer cells could direct the tumor-encountered T cells toward the Th2/Tc2 polarity. Cancer cells promote the production of IL-4 and down-regulate the production of IFN-γ in cancer-encountered T cells. The regulatory effects of cervical cancer cells are mediated mainly by IL-10, and TGF-β plays only a synergistic role. The cancer-derived effects can be reversed by neutralizing anti-IL-10 and anti-TGF-β Abs. IL-10 and TGF-β are present in cancer tissue and weakly expressed in precancerous tissue, but not in normal cervical epithelial cells. Our study strongly suggests important regulatory roles of IL-10 and TGF-β in cancer-mediated immunosuppression.

Original languageEnglish
Pages (from-to)2972-2978
Number of pages7
JournalJournal of Immunology
Volume167
Issue number5
DOIs
Publication statusPublished - Sep 1 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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