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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.

SUBMITTER: Kobayashi N

PROVIDER: S-EPMC3563854 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Oligodeoxynucleotides expressing polyguanosine motifs promote antitumor activity through the upregulation of IL-2.

Kobayashi Nobuaki N Hong Choongman C Klinman Dennis M DM Shirota Hidekazu H

Journal of immunology (Baltimore, Md. : 1950) 20130107 4

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 C ...[more]

PMID: 23296706

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