https://scholars.lib.ntu.edu.tw/handle/123456789/452549
Title: | Up-regulation of inhibitory natural killer receptors CD94/NKG2A with suppressed intracellular perforin expression of tumor-infiltrating CD8 + T lymphocytes in human cervical carcinoma | Authors: | BOR-CHING SHEU Chiou S.-H. HO-HSIUNG LIN SONG-NAN CHOW Huang S.-C. HONG-NERNG HO Hsu S.-M. |
Issue Date: | 2005 | Journal Volume: | 65 | Journal Issue: | 7 | Start page/Pages: | 2921-2929 | Source: | Cancer Research | Abstract: | Inhibitory signals that govern the cytolytic functions of CD8+ T lymphocytes have been linked to the expression of natural killer cell receptors (NKRs) on CTLs. There is limited knowledge about the induction of inhibitory NKR (iNKR) expression in vivo. Up-regulation of iNKRs has been linked to the modulation of the virus- and/or tumor-specific immune responses in animal models. In the present study, we directly examined the expression of various NKRs on tumor-infiltrating lymphocytes (TILs) derived from human cervical cancer. We found that in human cervical cancer, the percentage expression of immunoglobulin-like NKR+CD8+ T lymphocytes were similar in gated CD8+-autologous TILs and peripheral blood mononuclear cells. On the contrary, cervical cancer-infiltrating CD8+ T lymphocytes expressed up-regulated C-type lectin NKRs CD94/NKG2A compared with either peripheral blood CD8+ T cells or normal cervix-infiltrating CD8 + T lymphocytes. Dual NKR coexpression analyses showed that CD94 and NKG2A were mainly expressed on CD56-CD161-CD8+ TILs within the cancer milieu. Immunohistochemical study showed that cervical cancer cells expressed abundant interleukin 15 (IL-15) and transforming growth factor-β (TGF-β). In kinetic coculture assay, cervical cancer cells can promote the expression of CD94/NKG2A on CD8+ T lymphocytes. The cancer-derived effects can be reversed by addition of rIL-15Rα/Fc and anti-TGF-β antibody. Functional analyses illustrated that intracellular perforin expression of CD8+ T cells was minimal upon up-regulation of CD94/NKG2A. Kinetic cytotoxicity assays showed that up-regulated expressions of CD94/NKG2A restrain CD8+ T lymphocyte cytotoxicity. Our study strongly indicated that cervical cancer cells could promote the expression of iNKRs via an IL-15- and possibly TGF-β-mediated mechanism and abrogate the antitumor cytotoxicity of TILs. ?2005 American Association for Cancer Research. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-16844368435&doi=10.1158%2f0008-5472.CAN-04-2108&partnerID=40&md5=6afef73daee806145e8cdf54c9965227 https://scholars.lib.ntu.edu.tw/handle/123456789/452549 |
DOI: | 10.1158/0008-5472.CAN-04-2108 | SDG/Keyword: | CD8 antigen; CD94 antigen; interleukin 15; lectin; membrane receptor; natural killer cell receptor nkg 2 a; perforin; recombinant cytokine; recombinant interleukin 15 receptor alpha; transforming growth factor beta; transforming growth factor beta antibody; unclassified drug; article; cancer infiltration; cell assay; coculture; controlled study; cytolysis; cytopathogenic effect; cytotoxic T lymphocyte; human; human tissue; immunohistochemistry; lymphocyte culture; mixed lymphocyte culture; natural killer cell; peripheral blood mononuclear cell; priority journal; protein expression; tumor associated leukocyte; upregulation; uterine cervix carcinoma; Antigens, CD; Antigens, CD94; CD8-Positive T-Lymphocytes; Cytotoxicity, Immunologic; Female; Humans; Interleukin-15; Lectins, C-Type; Lymphocyte Culture Test, Mixed; Lymphocytes, Tumor-Infiltrating; Membrane Glycoproteins; Pore Forming Cytotoxic Proteins; Receptors, Immunologic; Recombinant Proteins; T-Lymphocytes, Cytotoxic; Transforming Growth Factor beta; Up-Regulation; Uterine Cervical Neoplasms |
Appears in Collections: | 醫學系 |
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