Selective expression of inhibitory Fcgamma receptor by metastatic melanoma impairs tumor susceptibility to IgG-dependent cellular response.

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 (FcgammaR) expressed by immune cells. We previously reported in a limited study that some human metastatic melanoma cells ectopically express the FcgammaRIIB1, an inhibitory isoform of FcgammaR. By analyzing a large panel of different types of human primary and metastatic solid tumors, we report herein that expression of FcgammaRIIB is restricted to melanoma and is acquired during tumor progression. We show that FcgammaRIIB 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 FcgammaRIIB. Using experimental mouse models, we demonstrate that expression of FcgammaRIIB protects B16F0 melanoma tumors from the ADCC induced by monoclonal and polyclonal anti-tumor IgG in vivo. Thus, our results identify FcgammaRIIB as a marker of human metastatic melanoma that impairs the tumor susceptibility to FcgammaR-dependent innate effector responses.

• Authors: Lydie Cassard, Joel F G Cohen-Solal, Emilie M Fournier, Sophie Camilleri-Broët, Alain Spatz, Salem Chouaïb, Cécile Badoual, Audrey Varin, Sylvain Fisson, Pierre Duvillard, Charlotte Boix, Shannon M Loncar, Xavier Sastre-Garau, Alan N Houghton, Marie-Françoise Avril, Ion Gresser, Wolf H Fridman, Catherine Sautès-Fridman
• Journal: International journal of cancer (Int J Cancer) Vol. 123 Issue 12 Pg. 2832-9 (Dec 15 2008) ISSN: 1097-0215 [Electronic] United States
• PMID: 18798552 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• Biomarkers, Tumor
• Fc gamma receptor IIB
• Immunoglobulin G
• Receptors, IgG

Topics

• Animals
• Biomarkers, Tumor (analysis)
• Cell Line, Tumor
• Disease Progression
• Flow Cytometry
• Gene Expression Regulation, Neoplastic
• Humans
• Immunoglobulin G (immunology)
• Immunohistochemistry
• Melanoma (immunology, secondary)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, SCID
• Receptors, IgG (analysis)
• Skin Neoplasms (immunology, pathology)