Alpha-fetoprotein impairs APC function and induces their apoptosis.
alpha-Fetoprotein (AFP) is a tumor-associated Ag, and its serum level is elevated in patients with hepatocellular carcinoma (HCC). In vitro, AFP induces functional impairment of dendritic cells (DCs). This was demonstrated by the down-regulation of CD40 and CD86 molecules and the impairment of allostimulatory function. Also, AFP was found to induce significant apoptosis of DCs, and AFP-treated DCs produced low levels of IL-12 and TNF-alpha, a cytokine pattern that could hamper an efficient antitumor immune response. Ex vivo, APCs of patients with HCC and high levels of AFP produced lower levels of TNF-alpha than that of healthy individuals. In conclusion, these results illustrate that AFP induces dysfunction and apoptosis of APCs, thereby offering a mechanism by which HCC escapes immunological control.
Um
Soon Ho
SH
Institute of Hepatology, University College London, United Kingdom.
Mulhall
Catherine
C
Alisa
Akeel
A
Ives
Annette Robyn
AR
Karani
John
J
Williams
Roger
R
Bertoletti
Antonio
A
Behboudi
Shahriar
S
D017951:Antigen Presentation / Q000187:drug effects*; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000494:pharmacology* / Q000502:physiology; D019139:Tumor Escape / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000509:alpha-Fetoproteins / Q000494:pharmacology* / Q000502:physiology
D000951:Antigens, Neoplasm; D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D000509:alpha-Fetoproteins; D018664:Interleukin-12