Abstract 4777: Human suppressor of cytokine signaling 1 controls immunostimulatory activity of monocyte-derived dendritic cells

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Dendritic cell (DC)-based tumor vaccines have only achieved limited clinical efficacy, underscoring the limitation of stimulatory strategies to elicit effective cytotoxic T lymphocyte (CTL) responses against self-tumor-associated antigens. Here, we investigate the role of human suppressor of cytokine signaling 1 (SOCS1), a feedback inhibitor of the Janus-activated kinase/signal transducer and activator of transcription signaling pathway, in regulating antigen presentation by human DCs (hDC). We find that human SOCS1 (hSOCS1)-silenced DCs have an enhanced stimulatory ability to prime self-antigen-specific CTLs in vitro and in a severe combined immunodeficient-hu mouse model. Human CTLs activated by SOCS1-silenced DCs, but not wild-type DCs, have an active lytic activity to natural antigen-expressing tumor cells. We further find that the capacity of hDCs to prime CTLs is likely controlled by SOCS1-restricted production and signaling of proinflammatory cytokines, such as interleukin-12. These results indicate a critical role of hSOCS1 in negatively regulating the immunostimulatory capacity of DCs and imply a translational potential of this alternative SOCS1 silencing strategy to develop effective DC vaccines. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4777.