| Abstract: |
During melanoma progression, patients develop anti-tumor immunity including the production of anti-tumor antibodies. Although the strategies developed by malignant cells to escape anti-tumor cellular immunity have been extensively investigated, little is known about tumor resistance to humoral immunity. The main effect of IgG antibodies is to activate the immune response by binding to host Fc gamma receptors (FcγR) expressed by immune cells. We previously reported in a limited study that some human metastatic melanoma cells ectopically express the FcγRIIB1, an inhibitory isoform of FcγR. By analyzing a large panel of different types of human primary and metastatic solid tumors, we report herein that expression of FcγRIIB is restricted to melanoma and is acquired during tumor progression. We show that FcγRIIB expression prevents the lysis of human metastatic melanoma cells by NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro, independently of the intracytoplasmic region of FcγRIIB. Using experimental mouse models, we demonstrate that expression of FcγRIIB protects B16F0 melanoma tumors from the ADCC induced by monoclonal and polyclonal anti-tumor IgG in vivo. Thus, our results identify FcγRIIB as a marker of human metastatic melanoma that impairs the tumor susceptibility to FcγR-dependent innate effector responses. © 2008 Wiley-Liss, Inc. |
| Keywords: |
immunohistochemistry; controlled study; protein expression; human cell; nonhuman; flow cytometry; animal cell; mouse; animals; mice; cancer susceptibility; melanoma; metastasis; skin neoplasms; tumor markers, biological; animal experiment; animal model; in vivo study; cytotoxicity; in vitro study; mice, scid; cell line, tumor; mice, inbred balb c; mice, inbred c57bl; gene expression regulation, neoplastic; immune response; immunoglobulin g; disease progression; tumor cell; melanoma b16; natural killer cell; innate immunity; receptors, igg; antibodies; tumor growth; fc receptor iib; immunoglobulin g antibody; immunocompetent cell; antibody dependent cellular cytotoxicity; immune escape; fc receptors; polyclonal antibody
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