Tumor-associated macrophages as a source of functional dendritic cells in ovarian cancer patients.
We have generated dendritic cells (DCs) from tumor-associated macrophages (TAMs) obtained from ascites fluid or tumor specimens of ovarian cancer patients, and compared them phenotypically and functionally to DCs derived from the patients' peripheral blood mononuclear cells (PBMCs). Both immature and mature DCs could be generated from TAMs. However, TAM-derived DCs underwent maturation to a lesser degree than PBMC-derived DCs, as measured by DC receptor surface expression. Nonetheless, in allogeneic mixed lymphocyte reactions, TAM-derived DCs stimulated T cell proliferation as efficiently as PBMC-derived DCs. In addition, TAM-derived DCs presenting tumor Ags were capable of stimulating IFN-gamma secretion by tumor-specific T cell lines. Thus, TAMs isolated from ovarian cancer patients can be used to generate significant numbers of DCs. Therefore, TAMs have potential use for either ex vivo or in vivo DC-based immunotherapy, particularly in individuals in which more conventional sources of DCs have been depleted.
Chu
Christina S
CS
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Woo
Edward Y
EY
Toll
Alanna J
AJ
Rubin
Stephen C
SC
June
Carl H
CH
Carroll
Richard G
RG
Schlienger
Katia
K
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma