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.

黑色素瘤是一种侵袭性皮肤癌，因为它具有高转移能力和对治疗的抵抗力。黑色素瘤细胞存在于异质的肿瘤微环境中，是其进展的关键调节因子。Snail1 是一种上皮-间质转化转录因子，在发育过程中表达，并在纤维化和癌症等病理情况下重新激活。在这项工作中，我们证明 Snail1 在黑色素瘤微环境中被激活，特别是在成纤维细胞中。对允许基质 Snail1 耗竭和治疗性 Snail1 阻断的小鼠模型的分析表明，针对肿瘤微环境中的 Snail1 可以减少黑色素瘤的生长和肺转移负担，从而延长小鼠的生存期。黑色素瘤相关成纤维细胞的转录组分析和肿瘤分析表明，基质 Snail1 通过促进免疫抑制微环境和抗肿瘤免疫力下降来诱导黑色素瘤生长。这项研究揭示了 Snail1 在黑色素瘤生物学中的新作用，并支持其作为治疗靶点的潜力。