Antibodies to placental immunoregulatory ferritin with transfer of polyclonal lymphocytes arrest MCF-7 human breast cancer growth in a nude mouse model.
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 effect was observed only in those transfused with human peripheral blood mononuclear cells. Blocking PLIF in tumor-engrafted human immune cell transfused mice resulted in massive 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-gamma 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.
Halpern
Marisa
M
Department of Pathology, Hasharon Hospital, Rabin Medical Center, Petah Tiqwa, Israel.
Zahalka
Muayad A
MA
Traub
Leonid
L
Moroz
Chaya
C
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005293:Ferritins / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000627:therapeutic use*; D016130:Immunophenotyping; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D011257:Pregnancy Proteins / Q000276:immunology*; D011817:Rabbits
D007074:Immunoglobulin G; D011257:Pregnancy Proteins; C491755:placental immunomodulatory ferritin protein, mouse; D016753:Interleukin-10; D007371:Interferon-gamma; D005293:Ferritins; D017493:Leukocyte Common Antigens