title: Properties of monocytes generated from haematopoietic CD34(+) stem cells from bone marrow of colon cancer patients.
abstract: Monocytes exhibit direct and indirect antitumour activities and may be potentially useful for various forms of adoptive cellular immunotherapy of cancer. However, blood is a limited source of them. This study explored whether monocytes can be obtained from bone marrow haematopoietic CD34(+) stem cells of colon cancer patients, using previously described protocol of expansion and differentiation to monocytes of cord blood-derived CD34(+) haematopoietic progenitors. Data show that in two-step cultures, the yield of cells was increased approximately 200-fold, and among these cells, up to 60 % of CD14(+) monocytes were found. They consisted of two subpopulations: CD14(++)CD16(+) and CD14(+)CD16(-), at approximately 1:1 ratio, that differed in HLA-DR expression, being higher on the former. No differences in expression of costimulatory molecules were observed, as CD80 was not detected, while CD86 expression was comparable. These CD14(+) monocytes showed the ability to present recall antigens (PPD, Candida albicans) and neoantigens expressed on tumour cells and tumour-derived microvesicles (TMV) to autologous CD3(+) T cells isolated from the peripheral blood. Monocytes also efficiently presented the immunodominant HER-2/neu369-377 peptide (KIFGSLAFL), resulting in the generation of specific cytotoxic CD8(+) T lymphocytes (CTL). The CD14(++)CD16(+) subset exhibited enhanced cytotoxicity, though nonsignificant, towards tumour cells in vitro. These observations indicate that generation of monocytes from CD34(+) stem cells of cancer patients is feasible. To our knowledge, it is the first demonstration of such approach that may open a way to obtain autologous monocytes for alternative forms of adaptive and adoptive cellular immunotherapy of cancer.
authors.affiliation: Department of Clinical Immunology and Transplantation, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, Wielicka str. 265, 30-663, Cracow, Poland. malgorzata.stec@uj.edu.pl
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Stec
authors.forename: Jarosław
authors.initials: J
authors.lastname: Baran
authors.forename: Rafał
authors.initials: R
authors.lastname: Szatanek
authors.forename: Bożenna
authors.initials: B
authors.lastname: Mytar
authors.forename: Marzena
authors.initials: M
authors.lastname: Lenart
authors.forename: Antoni
authors.initials: A
authors.lastname: Czupryna
authors.forename: Antoni
authors.initials: A
authors.lastname: Szczepanik
authors.forename: Maciej
authors.initials: M
authors.lastname: Siedlar
authors.forename: Marek
authors.initials: M
authors.lastname: Zembala
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D017452:Receptors, IgG / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D018952:Antigens, CD34; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG; C428200:FCGR3B protein, human; C508053:ERBB2 protein, human