Selective expression of inhibitory Fcgamma receptor by metastatic melanoma impairs tumor susceptibility to IgG-dependent cellular response.
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.
Cassard
Lydie
L
INSERM, U872, Microenvironnement immunitaire et tumeurs, Equipe 13, Centre de Recherche des Cordeliers, Paris, France.
Cohen-Solal
Joel F G
JF
Fournier
Emilie M
EM
Camilleri-Broët
Sophie
S
Spatz
Alain
A
Chouaïb
Salem
S
Badoual
Cécile
C
Varin
Audrey
A
Fisson
Sylvain
S
Duvillard
Pierre
P
Boix
Charlotte
C
Loncar
Shannon M
SM
Sastre-Garau
Xavier
X
Houghton
Alan N
AN
Avril
Marie-Françoise
MF
Gresser
Ion
I
Fridman
Wolf H
WH
Sautès-Fridman
Catherine
C
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007150:Immunohistochemistry; D008545:Melanoma / Q000276:immunology* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D017452:Receptors, IgG / Q000032:analysis*; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology
D014408:Biomarkers, Tumor; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D017452:Receptors, IgG