Silencing of SOCS1 enhances antigen presentation by dendritic cells and antigen-specific anti-tumor immunity
- 21 November 2004
- journal article
- Published by Springer Nature in Nature Biotechnology
- Vol. 22 (12) , 1546-1553
- https://doi.org/10.1038/nbt1035
Abstract
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.Keywords
This publication has 32 references indexed in Scilit:
- Co-inhibitory molecules of the B7–CD28 family in the control of T-cell immunityNature Reviews Immunology, 2004
- TheRole ofSuppressors ofCytokineSignaling(SOCS) Proteins inRegulation of theImmuneResponseAnnual Review of Immunology, 2004
- Suppressors of cytokine signaling and immunityNature Immunology, 2003
- Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanomaProceedings of the National Academy of Sciences, 2003
- Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patientsProceedings of the National Academy of Sciences, 2003
- Does the Immune System See Tumors as Foreign or Self?Annual Review of Immunology, 2003
- Tolerogenic Dendritic CellsAnnual Review of Immunology, 2003
- T-cell regulation by CD28 and CTLA-4Nature Reviews Immunology, 2001
- SOCS1 Is a Critical Inhibitor of Interferon γ Signaling and Prevents the Potentially Fatal Neonatal Actions of this CytokineCell, 1999
- Dendritic Cell Vaccines for Cancer ImmunotherapyAnnual Review of Medicine, 1999