Journal Article Ppublish
PubMed: 40898695 DOI: 10.1111/exd.70159
Targeting Melanin Heterogeneity in Metastatic Melanoma: A Dual-Tumour Mouse Melanoma Model.
Exp Dermatol 34(9):e70159
Authors: Marine Delmas, Benjamin Chaussin, Nathan Harismendy, Aurore Dougé, Paul-Olivier Rouzaire, Christopher Montemagno, Jérôme Durivault, Emmanuel Moreau, Elisabeth Miot-Noirault, Mercedes Quintana, Sophie Besse, Michel D'Incan, Emmanuel Chautard, Elodie Jouberton, Jacques Rouanet
Affiliations
- UMR1240 INSERM, Université Clermont Auvergne, Clermont-Ferrand, France. Centre Jean PERRIN, Service de Médecine Nucléaire, Clermont-Ferrand, France.
- UMR1240 INSERM, Université Clermont Auvergne, Clermont-Ferrand, France.
- Service d'Oncologie Médicale, CHU Gabriel Montpied, Clermont-Ferrand, France.
- Laboratoire HLA, CHU Gabriel Montpied, Clermont-Ferrand, France.
- Département de Biologie Médicale, Centre Scientifique de Monaco, Monaco, France.
- Service de Dermatologie et d'Oncodermatologie, CHU Estaing, Clermont-Ferrand, France.
- Centre Jean PERRIN, Service de Pathologie, Clermont-Ferrand, France.
- Centre Jean PERRIN, Service de Médecine Nucléaire, Clermont-Ferrand, France.
Abstract
The combination of melanin-targeted radionuclide therapy (TRT) and immunotherapy offers potential in overcoming melanoma resistance to conventional therapies. Studying the potential abscopal effect induced by TRT is essential to evaluate such combination. We develop here a preclinical murine model comprising a target (pigmented) and non-target (non-pigmented) tumour to study the abscopal effect induced by melanin-TRT in melanoma. Murine melanoma cell lines were tested: two pigmented (B16-F10 and B16-OVA) and one non-pigmented (B16-G4F), inoculated in C57BL/6 mice to assess pigmentation levels and immune infiltration. Heterogeneous tumour growth and repigmentation of the B16-G4F tumour led us to develop a non-pigmented cell line (B16-OVAmTYR-/-) by tyrosinase invalidation using CRISPR/Cas9. A dual-tumour model comprising the B16-OVA tumour and the B16-OVAmTYR tumour was evaluated in terms of tumour growth, pigmentation, and immune infiltrate. The B16-OVA model displayed homogeneous tumour growth, pigmentation and high immune infiltrate (CD8+ T cells p < 0.001; CD4+ T cells p < 0.05, regulatory T cells p < 0.001). The new B16-OVAmTYR-/- cell line ensured a consistent genetic background for comparative studies. The B16-OVAmTYR-/- maintained a non-pigmented phenotype without repigmentation (no melanin expression) and demonstrated similar tumour growth characteristics to its pigmented counterpart (DT = 2.4 ± 0.5 days). Establishing a dual-tumour model using both B16-OVA and B16-OVAmTYR-/- cell lines enabled concurrent study of pigmented and non-pigmented tumours in a single host, closely mirroring clinical scenarios of metastatic melanoma. We have successfully developed a new dual-tumour pigmented and non-pigmented mouse melanoma model mimicking clinical observations to study the abscopal effect in metastatic melanoma.
MeSH
Skin, Cells, Growth, Melanins, Melanoma, Skin Diseases, Immunotherapy, Cell Line, Therapeutics, Pigmentation