title: A population of HLA-DR+ immature cells accumulates in the blood dendritic cell compartment of patients with different types of cancer.
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-gamma 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.
authors.affiliation: Dendritic Cell and Cancer Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pinzon-Charry
authors.forename: Christopher S K
authors.initials: CS
authors.lastname: Ho
authors.forename: Richard
authors.initials: R
authors.lastname: Laherty
authors.forename: Tammy
authors.initials: T
authors.lastname: Maxwell
authors.forename: David
authors.initials: D
authors.lastname: Walker
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gardiner
authors.forename: Linda
authors.initials: L
authors.lastname: O'Connor
authors.forename: Christopher
authors.initials: C
authors.lastname: Pyke
authors.forename: Chris
authors.initials: C
authors.lastname: Schmidt
authors.forename: Colin
authors.initials: C
authors.lastname: Furnival
authors.forename: José Alejandro
authors.initials: JA
authors.lastname: López
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005910:Glioma / Q000097:blood* / Q000473:pathology; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000276:immunology; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; D007371:Interferon-gamma