title: Oligodeoxynucleotides expressing polyguanosine motifs promote antitumor activity through the upregulation of IL-2.
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.
authors.affiliation: Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Choongman
authors.initials: C
authors.lastname: Hong
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Shirota
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics / Q000276:immunology; D006151:Guanosine / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D006151:Guanosine