HLA-DR+ immature cells exhibit reduced antigen presenting cell function but respond to CD40 stimulation

Pinzon-Charry, Alberto, Maxwell, Tammy, Prato, Sandro, Furnival, Colin, Schmidt, Chris and Lopez, Jose Alejandro (2005) HLA-DR+ immature cells exhibit reduced antigen presenting cell function but respond to CD40 stimulation. Neoplasia, 7 12: 1123-1132. doi:10.1593/neo.05448


Author Pinzon-Charry, Alberto
Maxwell, Tammy
Prato, Sandro
Furnival, Colin
Schmidt, Chris
Lopez, Jose Alejandro
Title HLA-DR+ immature cells exhibit reduced antigen presenting cell function but respond to CD40 stimulation
Journal name Neoplasia   Check publisher's open access policy
ISSN 1522-8002
1476-5586
Publication date 2005-12-01
Sub-type Article (original research)
DOI 10.1593/neo.05448
Open Access Status DOI
Volume 7
Issue 12
Start page 1123
End page 1132
Total pages 10
Place of publication Ann Arbor, MI, United States
Publisher Neoplasia Press
Language eng
Subject 110709 Tumour Immunology
Abstract Dendritic cells (DC) have been implicated in the defective function of the immune system during cancer progression. We have demonstrated that patients with cancer have fewer myeloid (CD11c+DC) and lymphoid (CD123hiDC) DC and a concurrent accumulation of CD11c-CD123- immature cells expressing HLA-DR (DR+IC). Notably, DR+IC from cancer patients have a reduced capacity to stimulate allogeneic T-cells. DR+IC are also present in healthy donors, albeit in smaller numbers. In this study we assessed whether DR+IC could have an impact on the immune response by comparing their function with the DC counterparts. For this purpose, DR+IC and DC were purified from healthy donors and tested in several systems, including CTL priming, and the presentation of exogenous antigen through MHC-II and MHC-I molecules. DR+IC were less efficient than DC at presenting antigen to T-cells. DR+IC induced limited activation of T-cells, eliciting poor Th1 and preferentially inducing a Th2 bias in T-cells. Interestingly, despite DR+ICÂ’s poor responsiveness to inflammatory factors, CD40 ligation induced phenotypic maturation and IL-12 secretion, in turn, generating more efficient T-cell responses. These data underscore the importance of inefficient antigen presentation as a mechanism for tumor evasion and suggest an approach to improve the efficacy of DC-based immunotherapy for cancer.
Keyword Antigen-presenting cell
Dendritic cell subsets
CD40 ligand
Apoptosis
Immune dysfunction
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 12 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 11 Feb 2009, 19:46:27 EST by Ms Sarada Rao on behalf of School of Chemistry & Molecular Biosciences