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Microenvironmental Snail1-induced immunosuppression promotes melanoma growth
Marta Arumi-Planas1, Francisco Javier Rodriguez-Baena1, Francisco Cabello-Torres1
1Instituto de Neurociencias (CSIC-UMH), Sant Joan d'Alacant, Spain.
Abstract:
Melanoma is an aggressive form of skin cancer due to its high metastatic abilities and resistance to therapies. Melanoma cells reside in a heterogeneous tumour microenvironment that acts as a crucial regulator of its progression. Snail1 is an epithelial-to-mesenchymal transition transcription factor expressed during development and reactivated in pathological situations including fibrosis and cancer. In this work, we show that Snail1 is activated in the melanoma microenvironment, particularly in fibroblasts. Analysis of mouse models that allow stromal Snail1 depletion and therapeutic Snail1 blockade indicate that targeting Snail1 in the tumour microenvironment decreases melanoma growth and lung metastatic burden, extending mice survival. Transcriptomic analysis of melanoma-associated fibroblasts and analysis of the tumours indicate that stromal Snail1 induces melanoma growth by promoting an immunosuppressive microenvironment and a decrease in anti-tumour immunity. This study unveils a novel role of Snail1 in melanoma biology and supports its potential as a therapeutic target.
Insights
Targeting Snail1 in the melanoma microenvironment, particularly in fibroblasts, reduces tumor growth and metastasis. This approach enhances anti-tumor immunity, offering a new therapeutic strategy for aggressive skin cancer.
Area of Science:
- Oncology
- Cancer Biology
- Immunology
Background:
- Melanoma is an aggressive skin cancer known for high metastatic potential and treatment resistance.
- The tumor microenvironment significantly influences melanoma progression.
- Snail1, a transcription factor, is involved in development and reactivated in pathological conditions like cancer.
Purpose of the Study:
- To investigate the role of Snail1 activation within the melanoma microenvironment.
- To determine the therapeutic potential of targeting Snail1 in melanoma treatment.
Main Methods:
- Analysis of mouse models with stromal Snail1 depletion.
- Assessment of therapeutic Snail1 blockade.
- Transcriptomic analysis of melanoma-associated fibroblasts.
- Tumor microenvironment and anti-tumor immunity evaluation.
Main Results:
- Snail1 is activated in the melanoma microenvironment, especially in fibroblasts.
- Targeting stromal Snail1 reduced melanoma growth and lung metastasis.
- Stromal Snail1 blockade extended survival in mouse models.
- Snail1 promotes an immunosuppressive microenvironment, decreasing anti-tumor immunity.
Conclusions:
- Stromal Snail1 plays a critical role in melanoma progression by fostering an immunosuppressive environment.
- Targeting Snail1 in the tumor microenvironment represents a promising therapeutic strategy for melanoma.
- This study highlights Snail1 as a novel therapeutic target for aggressive skin cancer.
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