Abstract
The recently cloned human gene named "placental immunoregulatory ferritin" (PLIF ) is a pregnancy-related immunomodulator. Recombinant PLIF and its bioactive domain C48 are immune-suppressive and induce pronounced IL-10 production by immune cells. PLIF is expressed in the placenta and breast cancer cells. Blocking PLIF in pregnant mice by anti-C48 antibodies inhibited placental and fetal growth and modulated the cytokine network. It has been revealed that anti-C48 treatment inhibited MCF-7 tumor growth in nude mice. However, this significant effectwas observed only in those transfused with human peripheral blood mononuclear cells. Blocking PLIF in tumor-engrafted human immune cell transfusedmice resulted inmassive infiltration of human CD45+ cells (mainly CD8+ T cells), both intratumorally and in the tumor periphery, and a significant number of caspase-3+ cells. In vitro, anti-C48 treatment of MCF-7 tumor cells cocultured with human lymphocytes induced a significant increase in interferon-γ secretion. We conclude that blocking PLIF inhibits breast cancer growth, possibly by an effect on the cytokine network in immune cells and on breakdown of immunosuppression.
Original language | English |
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Pages (from-to) | 487-494 |
Number of pages | 8 |
Journal | Neoplasia |
Volume | 9 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2007 |
Externally published | Yes |
Keywords
- Antibody
- Breast cancer
- Gene
- Immunomodulator
- Immunotherapy