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Updated: Jun 10, 2026
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Metastatic melanomas express inhibitory low affinity fc gamma receptor and escape humoral immunity
Joel F G Cohen-Solal1, Lydie Cassard, Emilie M Fournier
1INSERM, U872, Microenvironnement Immunitaire et Tumeurs, Equipe 13, Centre de Recherche des Cordeliers, 75006 Paris, France.
Abstract:
Our research, inspired by the pioneering works of Isaac Witz in the 1980s, established that 40% of human metastatic melanomas express ectopically inhibitory Fc gamma receptors (FcgammaRIIB), while they are detected on less than 5% of primary cutaneous melanoma and not on melanocytes. We demonstrated that these tumoral FcgammaRIIB act as decoy receptors that bind the Fc portion of antimelanoma IgG, which may prevent Fc recognition by the effector cells of the immune system and allow the metastatic melanoma to escape the humoral/natural immune response. The FcgammaRIIB is able to inhibit the ADCC (antibody dependent cell cytotoxicity) in vitro. Interestingly, the percentage of melanoma expressing the FcgammaRIIB is high (70%) in organs like the liver, which is rich in patrolling NK (natural killer) cells that exercise their antitumoral activity by ADCC. We found that this tumoral FcgammaRIIB is fully functional and that its inhibitory potential can be triggered depending on the specificity of the anti-tumor antibody with which it interacts. Together these observations elucidate how metastatic melanomas interact with and potentially evade humoral immunity and provide direction for the improvement of anti-melanoma monoclonal antibody therapy.
Insights
Metastatic melanomas express inhibitory Fc gamma receptors (FcgammaRIIB) to evade immune responses. This finding offers new strategies for improving melanoma antibody therapies.
Area of Science:
- Immunology
- Oncology
Background:
- Melanoma metastasis involves immune evasion mechanisms.
- Fc gamma receptors (FcgammaR) play a role in immune responses to cancer.
Purpose of the Study:
- To investigate the expression and function of Fc gamma receptors in melanoma.
- To understand how melanoma evades immune surveillance.
Main Methods:
- Immunohistochemistry to detect FcgammaRIIB expression in primary and metastatic melanoma.
- In vitro assays to assess the inhibitory function of tumoral FcgammaRIIB on antibody-dependent cell cytotoxicity (ADCC).
Main Results:
- 40% of metastatic melanomas ectopically express FcgammaRIIB, compared to <5% of primary melanomas and 0% of melanocytes.
- Tumoral FcgammaRIIB acts as a decoy receptor, binding anti-melanoma IgG and inhibiting immune effector cell recognition.
- FcgammaRIIB expression is high (70%) in the liver, an organ rich in natural killer (NK) cells mediating ADCC.
- Tumoral FcgammaRIIB is functional and can inhibit ADCC depending on antibody specificity.
Conclusions:
- Metastatic melanomas utilize FcgammaRIIB to escape humoral and natural immune responses.
- FcgammaRIIB expression provides a mechanism for melanoma to evade antibody-mediated therapies.
- Targeting FcgammaRIIB or optimizing antibody selection could enhance anti-melanoma immunotherapy.
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