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Selective expression of inhibitory Fcγ receptor by metastatic melanoma impairs tumor susceptibility to IgG‐dependent cellular response
Author(s) -
Cassard Lydie,
CohenSolal Joel F.G.,
Fournier Emilie M.,
CamilleriBroët Sophie,
Spatz Alain,
Chouaïb Salem,
Badoual Cécile,
Varin Audrey,
Fisson Sylvain,
Duvillard Pierre,
Boix Charlotte,
Loncar Shan M.,
SastreGarau Xavier,
Houghton Alan N.,
Avril MarieFrançoise,
Gresser Ion,
Fridman Wolf H.,
SautèsFridman Catherine
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23870
Subject(s) - antibody dependent cell mediated cytotoxicity , melanoma , fc receptor , immune system , cancer research , immunology , biology , antibody , monoclonal antibody , immunosurveillance
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.