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

• Published in: Nature biotechnology Vol. 22; no. 12; pp. 1546 - 1553
• Main Authors: Chen, Si-Yi, Shen, Lei, Evel-Kabler, Kevin, Strube, Randy
• Format: Journal Article
• Language: English
• Published: New York, NY Nature 01.12.2004; Nature Publishing Group
• Subjects: Adaptive immunity; Animals; Antigen presentation; Antigen Presentation - genetics; Antigen Presentation - immunology; Biological and medical sciences; Biotechnology; Bone marrow; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Differentiation; Cell Line, Tumor; Cytokines; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - transplantation; Fundamental and applied biological sciences. Psychology; Gene Silencing - immunology; Health. Pharmaceutical industry; Immunotherapy, Adoptive - methods; Industrial applications and implications. Economical aspects; Kinases; Lymphocytes; Melanoma - immunology; Melanoma - pathology; Melanoma - therapy; Mice; Mice, Inbred C57BL; Miscellaneous; Repressor Proteins - genetics; Repressor Proteins - metabolism; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling Proteins; Tumors; Vaccines; Antineoplastic agent; Antigen; Dendritic cell; Antigen presentation; Gene silencing; Regulation(control); Cytokine; Vaccine; Inhibition; Immunity
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt1035

Tumor vaccines represent a promising therapeutic approach, but thus far have achieved only limited success in the clinic. The major challenge is to find a means of overcoming inhibitory immune regulatory mechanisms and eliciting effective T-cell responses to antigens preferentially expressed by tumor cells. Here we show that the stimulatory capacity of dendritic cells (DCs) and the magnitude of adaptive immunity are critically regulated by the suppressor of cytokine signaling (SOCS) 1 in DCs. Silencing SOCS1 in antigen-presenting DCs strongly enhances antigen-specific anti-tumor immunity. Our findings indicate that SOCS1 represents an inhibitory mechanism for qualitatively and quantitatively controlling antigen presentation by DCs and the magnitude of adaptive immunity. This study has implications for understanding the regulation of antigen presentation and for developing more effective tumor vaccines by silencing the critical brake in antigen presentation.