Faculty Collaboration Database

Adenoviral-transduced dendritic cells are susceptible to suppression by T regulatory cells and promote interleukin 17 production. Cancer Immunol Immunother 2011 Mar;60(3):381-8

Date

12/15/2010

Pubmed ID

21153637

Pubmed Central ID

PMC11028621

DOI

10.1007/s00262-010-0948-4

Scopus ID

2-s2.0-79953817679 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

Dendritic cell (DC) vaccines offer a robust platform for the development of cancer vaccines, but their effectiveness is thought to be limited by T regulatory cells (Tregs). Recombinant adenoviruses (RAdV) have been used successfully to engineer tumor antigen expression in DCs, but the impact of virus transduction on susceptibility to suppression by Tregs is unknown. We investigated the functional consequences of exposure to adenovirus on interactions between human monocyte-derived DCs and Tregs. Since the development of Tregs is linked to that of pro-inflammatory Th17 cells, the role of Th17 cells and IL-17-producing Tregs in the context of DC-based immunotherapies was also investigated. We found that Tregs potently suppressed the co-stimulatory capacity of RAdV-transduced DCs, regardless of whether the DCs were maturated by inflammatory cytokines or by exposure to Th1 or Th17 cells. Furthermore, exposure of Tregs to RAdV-exposed DCs increased IL-17 production and suppressive capacity, and correlated with enhanced secretion of IL-1β and IL-6 by DCs. The findings that DCs exposed to RAdV are suppressed by Tregs, promote Treg plasticity, and enhance Treg suppression indicates that strategies to limit Tregs will be required to enhance the efficacy of such DC-based immunotherapies.

Author List

Wang AY, Crome SQ, Jenkins KM, Medin JA, Bramson JL, Levings MK

Author

Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenoviridae
Cancer Vaccines
Cell Differentiation
Cytokines
Dendritic Cells
Genetic Vectors
Humans
Immunotherapy
Interleukin-17
Interleukin-23
Lymphocyte Activation
T-Lymphocytes, Regulatory
Th17 Cells
Up-Regulation