title: Blood CD33(+)HLA-DR(-) myeloid-derived suppressor cells are increased with age and a history of cancer.
abstract: As we age, the composition of our peripheral leukocytes changes dramatically. Many of these alterations contribute to the general immune dysfunction that burdens the elderly, which in turn, contributes to increased susceptibility to disease. MDSCs represent a heterogeneous population of immunosuppressive leukocytes that are elevated in the peripheral blood of cancer patients. Given the relation between cancer incidence and age, this study examined the frequency of peripheral blood CD33(+)HLA-DR(-) MDSCs across three cohorts: healthy adults (19-59 years old), community-dwelling seniors (61-76 years old), and frail elderly (67-99 years old). This analysis is the first to demonstrate that MDSCs and specifically the CD11b(+)CD15(+) MDSC subset are increased with age. Proinflammatory cytokines that are required for the differentiation of MDSCs (e.g., TNF-α, IL-6, and IL-1β) were similarly found to be increased in the serum of the frail elderly. Furthermore, the proportion of MDSCs and the CD11b(+)CD15(+) subset were found to be elevated significantly in elderly donors with a history of cancer. This age-related elevation in the frequency of MDSCs may contribute to the increased cancer incidence that occurs with age. Further investigation into the functional consequences of elevated MDSCs will provide valuable insight into the progression of age-related pathologies.
authors: McMaster University, 1280 Main St. West, Hamilton, Ontario, Canada.
authors: Chris P
authors: CP
authors: Verschoor
authors: Jennie
authors: J
authors: Johnstone
authors: Jamie
authors: J
authors: Millar
authors: Michael G
authors: MG
authors: Dorrington
authors: Mojtaba
authors: M
authors: Habibagahi
authors: Alina
authors: A
authors: Lelic
authors: Mark
authors: M
authors: Loeb
authors: Jonathan L
authors: JL
authors: Bramson
authors: Dawn M E
authors: DM
authors: Bowdish
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000276:immunology / Q000473:pathology*; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D053583:Interleukin-1beta / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D016256:Lewis X Antigen / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009369:Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology*; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: D039481:CD11b Antigen; C571163:CD33 protein, human; D006684:HLA-DR Antigens; C508600:IL6 protein, human; C509295:ITGAM protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016256:Lewis X Antigen; D063268:Sialic Acid Binding Ig-like Lectin 3; D014409:Tumor Necrosis Factor-alpha; C066693:FUT4 protein, human; D005647:Fucosyltransferases