Silencing of SOCS1 enhances antigen presentation by dendritic cells and antigen-specific anti-tumor immunity

Nature biotechnology 22, 1546 - 1553 (2004)

Speaker: 林嬿琳                          Time: 14:00-15:00, May 18, 2005

Commentator: 蕭璦莉 老師                Place: Room601

Abstract :

SOCS1 functions as a negative regulator of signaling by various cytokines, such as interferon -g, interleukin-7 or IL-12, by inhibiting the Janus kinases (JAKs) in T cells and other immune cells.

 A recent study showed that SOCS1^-/- dendritic cells (DCs) were hyperresponsive to IFN-g and induced autoreactive antibody production,

 hinting at a role for SOCS1 in the negative regulation of DCs. Therefore, the author cloned SOCS1 siRNA or a control green fluorescent protein siRNA into a lentiviral vector. C57BL/6 mice were immunized with ovalbumin peptide-pulsed LV-SOCS1-siRNA or LV-GFP-siRNA DCs. The ability of SOCS1-silenced DCs to prime the antigen specific response was enhanced by detecting the percentage ovalbumin peptide–specific CD8⁺ T cells, IFN-g ELISPOT assay, the cytotoxicity response. These results were consistent with the findings in vitro. Accordingly, these data indicated SOCS1 negatively regulated the ability of antigen presentation of DCs to prime antigen-specific CD8⁺ T cell responses. Moreover, SOCS1 not only regulated immature DCs but also mature DCs. SOCS1 silencing permited greater responsiveness of matured DCs to endogenous environmental stimuli, leading to an enhanced CTL response. Finally, a murine melanocyte differentiation antigen tyrosinase-related protein (TRP) 2 is naturally expressed in the weakly immunogenic B16 melanoma cells. Immunization with TRP2 peptide-pulsed LV-SOCS1-siRNA-DCs with ex vivo maturation efficiently blocked the growth of pre-established B16 tumors, whereas mature LV-GFP-siRNA-DCs didn’t have this effect. These indicate silencing SOCS1 in antigen-presenting DCs strongly enhances the antigen-specific anti-tumor immunity. In future, DCs will be used to develop more effective tumor vaccines by silencing the critical brake in antigen presentation.

References :

1. Hanada, T. et al. Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity. Immunity 19, 437–450 (2003). 

2. Shen, L., Evel-Kaber, K., Strube, R. & Chen, S.Y. Silencing of SOCS1 enhances antigen presentation by dendritic cells and antigen-specific anti-tumor immunity. Nat. Biotechnol. 22, 1546−1553 (2004).