Abstract
Analysis of cytokine and chemokine production by tumor cell lines including five lung cancers, a malignant mesothelioma, and a malignant melanoma recently established in our laboratory showed rather high production of IL-8 in all tumors and IL-6 in one lung cancer, the malignant mesothelioma, and the malignant melanoma. We investigated the migration of PBMCs to these tumor cells using Transwell plates and showed enrichment of Foxp3(+) CD4 regulatory T cells (Tregs) in migrated T cells to both IL-6- and IL-8-producing tumors. Marked induction of CXCR1 expression on Foxp3(+) CD4 Tregs by IL-6 followed by IL-8-mediated migration appeared to be responsible for enriched migration. Frequent production of IL-8 by the tumors and Treg migration to those tumors through induction of IL-8R expression by IL-6 is one of the mechanisms for tumor escape.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / pathology
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Cell Line, Tumor
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Cell Movement / immunology*
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Forkhead Transcription Factors / biosynthesis*
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Humans
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Interleukin-6 / biosynthesis*
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Interleukin-6 / physiology
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Interleukin-8 / biosynthesis*
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Interleukin-8 / physiology
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Lung Neoplasms / immunology
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Lung Neoplasms / metabolism
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Melanoma / immunology
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Melanoma / metabolism
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Mesothelioma / immunology
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Mesothelioma / metabolism
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Receptors, Interleukin-8A / biosynthesis*
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Receptors, Interleukin-8A / physiology
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism*
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T-Lymphocytes, Regulatory / pathology
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Tumor Cells, Cultured
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Tumor Escape / immunology
Substances
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CXCL8 protein, human
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FOXP3 protein, human
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Forkhead Transcription Factors
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IL6 protein, human
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Interleukin-6
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Interleukin-8
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Receptors, Interleukin-8A