Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells

Yuko Shirota, Hidekazu Shirota, Dennis M. Klinman

Research output: Contribution to journalArticlepeer-review

153 Citations (Scopus)

Abstract

Immunostimulatory CpG oligonucleotides (ODN) activate cells that express TLR9 and have been shown to improve the host's response to tumor Ags. Unfortunately, the immunosuppressive microenvironment that surrounds many cancers inhibits Ag-specific cellular responses and thus interferes with CpG-mediated immunotherapy. Myeloid-derived suppressor cells (MDSC) represent an important constituent of this immunosuppressive milieu. Large numbers of MDSC are present in and near tumor sites where they inhibit the activity of Ag-specific T and NK cells. Current studies indicate that the delivery of CpG ODN directly into the tumor bed reduces the immunosuppressive activity of monocytic (CD11b +, Ly6G -, Ly6C high) MDSC. Monocytic MDSC express TLR9 and respond to CpG stimulation by 1) losing their ability to suppress T cell function, 2) producing Th1 cytokines, and 3) differentiating into macrophages with tumoricidal capability. These findings provide insight into a novel mechanism by which CpG ODN contribute to tumor regression, and they support intratumoral injection as the optimal route for their delivery.

Original languageEnglish
Pages (from-to)1592-1599
Number of pages8
JournalJournal of Immunology
Volume188
Issue number4
DOIs
Publication statusPublished - 2012 Feb 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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