Abstract
The primary goal of cancer immunotherapy is to elicit an immune response capable of eliminating the tumor. One approach toward accomplishing that goal uses general (rather than tumor-specific) immunomodulatory agents to boost the number and activity of pre-existing CTLs. We find that the intratumoral injection of polyguanosine (poly-G) oligonucleotides (ODN) has such an effect, boosting antitumor immunity and promoting tumor regression. The antitumor activity of poly-G ODN was mediated through CD8 T cells in a TLR9-independent manner. Mechanistically, poly-G ODN directly induced the phosphorylation of Lck (an essential element of the T cell-signaling pathway), thereby enhancing the production of IL-2 and CD8 T cell proliferation. These findings establish poly-G ODN as a novel type of cancer immunotherapy.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Amino Acid Motifs / genetics
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Amino Acid Motifs / immunology
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Animals
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Antineoplastic Agents / metabolism*
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Cell Line, Tumor
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CpG Islands / genetics
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CpG Islands / immunology
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Guanosine / biosynthesis
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Guanosine / genetics
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Guanosine / physiology*
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Humans
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Interleukin-2 / biosynthesis*
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Interleukin-2 / genetics
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, Transgenic
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Oligodeoxyribonucleotides / biosynthesis*
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Oligodeoxyribonucleotides / chemical synthesis
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Oligodeoxyribonucleotides / pharmacology*
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Phosphorylation / drug effects
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Phosphorylation / immunology
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / metabolism
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T-Lymphocytes, Cytotoxic / pathology
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Tumor Cells, Cultured
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Up-Regulation / genetics
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Up-Regulation / immunology*
Substances
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Antineoplastic Agents
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Interleukin-2
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Oligodeoxyribonucleotides
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Guanosine