A Population of HLA-DR⁺ Immature Cells Accumulates in the Blood Dendritic Cell Compartment of Patients with Different Types of Cancer

Authors: Pinzon-Charry, Alberto¹; Ho, Christopher S.K.²; Laherty, Richard³; Maxwell, Tammy¹; Walker, David⁴; Gardiner, Robert A.⁵; O'Connor, Linda¹; Pyke, Christopher⁶; Schmidt, Chris¹; Furnival, Colin⁷; López, José Alejandro⁸

Source: Neoplasia, Volume 7, Number 12, December 2005 , pp. 1112-1122(11)

Publisher: Neoplasia Press

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Abstract:

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c⁺) and plasmacytoid (CD123⁺) DC, and a concurrent accumulation of CD11c⁻CD123⁻ immature cells that expressed high levels of HLA-DR⁺ immature cells (DR⁺IC). Although DR⁺IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR⁺IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-γ secretion by T-lymphocytes. Importantly, increased numbers of DR⁺IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR⁺IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR⁺IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.

Keywords: Solid tumors; dendritic cell subsets; immune dysfunction; immature antigen-presenting cell; breast cancer

Document Type: Research article

DOI: 10.1593/neo.05442

Affiliations: 1: Dendritic Cell and Cancer Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia 2: Dendritic Cell Laboratory, Mater Medical Research Institute, Brisbane, Queensland 4101, Australia 3: Radiation Biology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia; Department of Neurosurgery, Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia 4: Department of Neurosurgery, Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia 5: Department of Surgery, Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia 6: Department of Surgery, Mater Misericordiae Hospital, Brisbane, Queensland 4101, Australia 7: Wesley Medical Centre, Brisbane, Queensland 4066, Australia 8: Dendritic Cell and Cancer Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia, Email: alejl@qimr.edu.au

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