Skip to main content

Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity.

Publication ,  Journal Article
Dannull, J; Lesher, D-T; Holzknecht, R; Qi, W; Hanna, G; Seigler, H; Tyler, DS; Pruitt, SK
Published in: Blood
December 15, 2007

The process of dendritic cell (DC) maturation, critical for effective DC-based immunotherapy, also alters the proteasome such that peptides presented in the context of HLA class I are generated not by the constitutive proteasome, but by the immunoproteasome. Cytotoxic T lymphocytes (CTLs) induced by such DCs might not optimally recognize tumor cells normally expressing the constitutive proteasome. Using small interfering RNA (siRNA) transfection of DCs to inhibit expression of the 3 inducible immunoproteasome subunits in mature DCs, we found that such DCs expressed increased intracellular levels of constitutive proteasomes and presented an altered repertoire of tumor-antigenic peptides. When DCs generated from the monocytes of 3 patients with melanoma were transfected with immunoproteasome siRNA, induced to mature, and then trans-fected with RNA encoding defined melanoma antigens, these DCs were superior inducers of antigen-specific CTLs against autologous melanoma cells. This alteration of DC proteasome composition, which enhances the ability of mature antigen-loaded DCs to stimulate anti-tumor immune responses, may lead to more effective DC-based tumor immunotherapy.

Duke Scholars

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

December 15, 2007

Volume

110

Issue

13

Start / End Page

4341 / 4350

Location

United States

Related Subject Headings

  • Transfection
  • T-Lymphocytes, Cytotoxic
  • RNA, Small Interfering
  • Proteasome Endopeptidase Complex
  • Melanoma
  • Immunotherapy
  • Immunology
  • Humans
  • Dendritic Cells
  • Cell Line, Tumor
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dannull, J., Lesher, D.-T., Holzknecht, R., Qi, W., Hanna, G., Seigler, H., … Pruitt, S. K. (2007). Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity. Blood, 110(13), 4341–4350. https://doi.org/10.1182/blood-2007-04-083188
Dannull, Jens, Diem-Thu Lesher, Robert Holzknecht, Wenning Qi, Gabi Hanna, Hilliard Seigler, Douglas S. Tyler, and Scott K. Pruitt. “Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity.Blood 110, no. 13 (December 15, 2007): 4341–50. https://doi.org/10.1182/blood-2007-04-083188.
Dannull J, Lesher D-T, Holzknecht R, Qi W, Hanna G, Seigler H, et al. Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity. Blood. 2007 Dec 15;110(13):4341–50.
Dannull, Jens, et al. “Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity.Blood, vol. 110, no. 13, Dec. 2007, pp. 4341–50. Pubmed, doi:10.1182/blood-2007-04-083188.
Dannull J, Lesher D-T, Holzknecht R, Qi W, Hanna G, Seigler H, Tyler DS, Pruitt SK. Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity. Blood. 2007 Dec 15;110(13):4341–4350.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

December 15, 2007

Volume

110

Issue

13

Start / End Page

4341 / 4350

Location

United States

Related Subject Headings

  • Transfection
  • T-Lymphocytes, Cytotoxic
  • RNA, Small Interfering
  • Proteasome Endopeptidase Complex
  • Melanoma
  • Immunotherapy
  • Immunology
  • Humans
  • Dendritic Cells
  • Cell Line, Tumor