Overcoming regulatory T-cell suppression by a lyophilized preparation of Streptococcus pyogenes Journal Article
| Authors: | Hirayama, M.; Nishikawa, H.; Nagata, Y.; Tsuji, T.; Kato, T.; Kageyama, S.; Ueda, S.; Sugiyama, D.; Hori, S.; Sakaguchi, S.; Ritter, G.; Old, L. J.; Gnjatic, S.; Shiku, H. |
| Article Title: | Overcoming regulatory T-cell suppression by a lyophilized preparation of Streptococcus pyogenes |
| Abstract: | Cancer vaccines have yet to yield clinical benefit, despite the measurable induction of humoral and cellular immune responses. As immunosuppression by CD4+CD25+ regulatory T (Treg) cells has been linked to the failure of cancer immunotherapy, blocking suppression is therefore critical for successful clinical strategies. Here, we addressed whether a lyophilized preparation of Streptococcus pyogenes (OK-432), which stimulates Toll-like receptors, could overcome Treg-cell suppression of CD4+ T-cell responses in vitro and in vivo. OK-432 significantly enhanced in vitro proliferation of CD4+ effector T cells by blocking Treg-cell suppression and this blocking effect depended on IL-12 derived from antigen-presenting cells. Direct administration of OK-432 into tumor-associated exudate fluids resulted in a reduction of the frequency and suppressive function of CD4+CD25+Foxp3+ Treg cells. Furthermore, when OK-432 was used as an adjuvant of vaccination with HER2 and NY-ESO-1 for esophageal cancer patients, NY-ESO-1-specific CD4+ T-cell precursors were activated, and NY-ESO-1-specific CD4+ T cells were detected within the effector/memory T-cell population. CD4+ T-cell clones from these patients had high-affinity TCRs and recognized naturally processed NY-ESO-1 protein presented by dendritic cells. OK-432 therefore inhibits Treg-cell function and contributes to the activation of high-avidity tumor antigen-specific naive T-cell precursors. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
| Keywords: | vaccination; tumor immunology; treg cells |
| Journal Title: | European Journal of Immunology |
| Volume: | 43 |
| Issue: | 4 |
| ISSN: | 0014-2980 |
| Publisher: | Wiley V C H Verlag Gmbh |
| Date Published: | 2013-04-01 |
| Start Page: | 989 |
| End Page: | 1000 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 23436617 |
| DOI: | 10.1002/eji.201242800 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2013" - "CODEN: EJIMA" - ":doi 10.1002/eji.201242800" - "Source: Scopus" |
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