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Updated: Sep 9, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Targeting Melanin Heterogeneity in Metastatic Melanoma: A Dual-Tumour Mouse Melanoma Model
Marine Delmas1,2, Benjamin Chaussin1, Nathan Harismendy1
1UMR1240 INSERM, Université Clermont Auvergne, 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.
Insights
Researchers developed a novel dual-tumour mouse model for melanoma, combining pigmented and non-pigmented tumors. This model aids in studying the abscopal effect of melanin-targeted radionuclide therapy (TRT) and immunotherapy in melanoma.
Area of Science:
- Oncology
- Immunology
- Preclinical Research
Background:
- Melanoma exhibits resistance to conventional therapies.
- Combination of radionuclide therapy (TRT) and immunotherapy shows promise for melanoma treatment.
- Understanding the abscopal effect of TRT is crucial for evaluating combination therapies.
Purpose of the Study:
- To develop a preclinical murine model for studying the abscopal effect of melanin-TRT in melanoma.
- To create a dual-tumour model with both pigmented and non-pigmented tumors to mimic clinical metastatic melanoma scenarios.
- To evaluate the efficacy of a novel non-pigmented melanoma cell line for consistent preclinical studies.
Main Methods:
- Development of a dual-tumour mouse model using B16-OVA (pigmented) and B16-OVAmTYR-/- (non-pigmented) melanoma cell lines.
- Utilized CRISPR/Cas9 for tyrosinase invalidation to create the non-pigmented cell line.
- Assessed tumor growth, pigmentation, and immune infiltration (CD8+, CD4+, regulatory T cells) in the developed model.
Main Results:
- The B16-OVA model showed homogeneous growth, pigmentation, and significant immune infiltration.
- The novel B16-OVAmTYR-/- cell line maintained a non-pigmented phenotype without repigmentation and exhibited similar growth rates to its pigmented counterpart.
- The dual-tumour model successfully allowed for the concurrent study of pigmented and non-pigmented tumors in a single host.
Conclusions:
- A novel dual-tumour mouse model for melanoma has been successfully established, comprising both pigmented and non-pigmented tumors.
- This model accurately mimics clinical observations in metastatic melanoma, facilitating the study of the abscopal effect.
- The developed model provides a valuable platform for investigating the combination of melanin-TRT and immunotherapy in melanoma treatment.
