Cytokines IL-1α, IL-6, and GM-CSF constitutively secreted by oral squamous carcinoma induce down-regulation of CD80 costimulatory molecule expression: restoration by interferon γ
| Autor: | Carter Van Waes, Judy Wen, Elena Leukinova, Zhong Chen, Giovana R. Thomas |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Cancer Research medicine.medical_treatment Immunology Down-Regulation Antineoplastic Agents Enzyme-Linked Immunosorbent Assay chemical and pharmacologic phenomena Biology Interferon-gamma Mice Gene expression medicine Animals Immunology and Allergy Interferon gamma RNA Messenger RNA Neoplasm Mice Inbred BALB C Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction Granulocyte-Macrophage Colony-Stimulating Factor hemic and immune systems Blotting Northern medicine.disease Head and neck squamous-cell carcinoma Recombinant Proteins Squamous carcinoma Disease Models Animal Cytokine Oncology Epidermoid carcinoma Tumor progression B7-1 Antigen Carcinoma Squamous Cell Cancer research Cytokines Mouth Neoplasms Cell Division CD80 Interleukin-1 medicine.drug |
| Zdroj: | Cancer Immunology, Immunotherapy. 53:33-40 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-003-0433-4 |
| Popis: | We previously characterized the expression of CD80 in different murine head and neck squamous cell carcinoma (HNSCC) clones derived following tumor progression in the absence of T cell-mediated immunity in severe combined immunodeficient (SCID) mice. We found that HNSCCs that did not express CD80 grew as progressors, while those that expressed CD80 were regressors when grown in immune-competent animals. In the present study, we characterized expression of a repertoire of immunoregulatory cytokines in these HNSCC lines, and found that HNSCCs that express cytokines IL-1 alpha, IL-6, and GM-CSF do not express CD80, suggesting the hypothesis that these cytokines may down-modulate expression of CD80. Cytokine-conditioned medium from progressor HNSCC and recombinant IL-1 alpha, IL-6, and GM-CSF caused a reduction of CD80 expression in regressor HNSCCs without affecting proliferation. Conversely, the decrease in CD80 expression in progressor HNSCCs could be restored by IFN-gamma, a known inducer of CD80 expression. These data strongly suggest that high levels of cytokines IL-1 alpha, IL-6, and GM-CSF expressed by tumor cells can down-regulate CD80 expression in HNSCC, and that IFN-gamma can independently stimulate expression. These data provide evidence for a novel mechanism of cytokine-mediated down-modulation of CD80 during malignant progression of HNSCC that can be restored by IFN-gamma. |
| Databáze: | OpenAIRE |
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