Oligodeoxynucleotides Expressing Polyguanosine Motifs Promote Antitumor Activity through the Upregulation of IL-2 | Zendy

Nobuaki Kobayashi | Zendy; Choongman Hong | Zendy; Dennis M. Klinman | Zendy; Hidekazu Shirota | Zendy

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Oligodeoxynucleotides Expressing Polyguanosine Motifs Promote Antitumor Activity through the Upregulation of IL-2

Author(s) -

Nobuaki Kobayashi,

Choongman Hong,

Dennis M. Klinman,

Hidekazu Shirota

Publication year - 2013

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.1201063

Subject(s) - cd8 , cancer immunotherapy , downregulation and upregulation , immunotherapy , cancer research , immune system , t cell , tlr9 , phosphorylation , cytotoxic t cell , biology , chemistry , immunology , microbiology and biotechnology , in vitro , biochemistry , gene , gene expression , dna methylation

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.

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