α-fetoprotein impairs APC function and induces their apoptosis

Soon Ho Um, Catherine Mulhall, Akeel Alisa, Annette Robyn Ives, John Karani, Roger Williams, Antonio Bertoletti, Shahriar Behboudi

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)

Abstract

α-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 molecnles 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-α, 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-α 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.

Original languageEnglish
Pages (from-to)1772-1778
Number of pages7
JournalJournal of Immunology
Volume173
Issue number3
DOIs
Publication statusPublished - 2004 Aug 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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