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

被引:222
作者
Shen, L
Evel-Kabler, K
Strube, R
Chen, SY
机构
[1] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[3] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA
关键词
D O I
10.1038/nbt1035
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:1546 / 1553
页数:8
相关论文
共 33 条
[11]   Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients [J].
Hodi, FS ;
Mihm, MC ;
Soiffer, RJ ;
Haluska, FG ;
Butler, M ;
Seiden, MV ;
Davis, T ;
Henry-Spires, R ;
MacRae, S ;
Willman, A ;
Padera, R ;
Jaklitsch, MT ;
Shankar, S ;
Chen, TC ;
Korman, A ;
Allison, JP ;
Dranoff, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (08) :4712-4717
[12]  
Huang XF, 2003, CANCER RES, V63, P7321
[13]   SOCS1/JAB is a negative regulator of LPS-induced macrophage activation [J].
Kinjyo, I ;
Hanada, T ;
Inagaki-Ohara, K ;
Mori, H ;
Aki, D ;
Ohishi, M ;
Yoshida, H ;
Kubo, M ;
Yoshimura, A .
IMMUNITY, 2002, 17 (05) :583-591
[14]   Suppressors of cytokine signaling and immunity [J].
Kubo, M ;
Hanada, T ;
Yoshimura, A .
NATURE IMMUNOLOGY, 2003, 4 (12) :1169-1176
[15]   Enhancement of antitumor immunity by CTLA-4 blockade [J].
Leach, DR ;
Krummel, MF ;
Allison, JP .
SCIENCE, 1996, 271 (5256) :1734-1736
[16]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408
[17]   SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality [J].
Marine, JC ;
Topham, DJ ;
McKay, C ;
Wang, DM ;
Parganas, E ;
Stravopodis, D ;
Yoshimura, A ;
Ihle, JN .
CELL, 1999, 98 (05) :609-616
[18]   Repetitive injections of dendritic cells matured with tumor necrosis factor α induce antigen-specific protection of mice from autoimmunity [J].
Menges, M ;
Rössner, S ;
Voigtländer, C ;
Schindler, H ;
Kukutsch, NA ;
Bogdan, C ;
Erb, K ;
Schuler, G ;
Lutz, MB .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (01) :15-21
[19]   The lethal effects of transplantation of Socs1-/- bone marrow cells into irradiated adult syngeneic recipients [J].
Metcalf, D ;
Mifsud, S ;
Di Rago, L ;
Alexander, WS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (14) :8436-8441
[20]   SOCS-1/SSI-1-deficient NKT cells participate in severe hepatitis through dysregulated cross-talk inhibition of IFN-γ and IL-4 signaling in vivo [J].
Naka, T ;
Tsutsui, H ;
Fujimoto, M ;
Kawazoe, Y ;
Kohzaki, H ;
Morita, Y ;
Nakagawa, R ;
Narazaki, M ;
Adachi, K ;
Yoshimoto, T ;
Nakanishi, K ;
Kishimoto, T .
IMMUNITY, 2001, 14 (05) :535-545