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Microenvironmental Snail1 is a driver of immunosuppression in melanoma

View ORCID ProfileMarta Arumi-Planas, View ORCID ProfileFrancisco Javier Rodriguez-Baena, Francisco Cabello-Torres, Francisco Gracia, Cristina Lopez-Blau, View ORCID ProfileM. Angela Nieto, View ORCID ProfileBerta Sanchez-Laorden
doi: https://doi.org/10.1101/2022.11.23.517623
Marta Arumi-Planas
1Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, 03550 Spain
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  • ORCID record for Marta Arumi-Planas
Francisco Javier Rodriguez-Baena
1Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, 03550 Spain
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  • ORCID record for Francisco Javier Rodriguez-Baena
Francisco Cabello-Torres
1Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, 03550 Spain
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Francisco Gracia
1Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, 03550 Spain
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Cristina Lopez-Blau
1Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, 03550 Spain
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M. Angela Nieto
1Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, 03550 Spain
2CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Spain
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Berta Sanchez-Laorden
1Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, 03550 Spain
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  • ORCID record for Berta Sanchez-Laorden
  • For correspondence: berta.lopez@umh.es
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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 murine models that allow stromal Snail1 depletion and therapeutic Snail1 blockade indicate that targeting Snail1 activation 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 pro-tumour immunity. This study unveils a novel role of Snail1 in melanoma biology and supports its potential as a therapeutic target.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 27, 2022.
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Microenvironmental Snail1 is a driver of immunosuppression in melanoma
Marta Arumi-Planas, Francisco Javier Rodriguez-Baena, Francisco Cabello-Torres, Francisco Gracia, Cristina Lopez-Blau, M. Angela Nieto, Berta Sanchez-Laorden
bioRxiv 2022.11.23.517623; doi: https://doi.org/10.1101/2022.11.23.517623
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Microenvironmental Snail1 is a driver of immunosuppression in melanoma
Marta Arumi-Planas, Francisco Javier Rodriguez-Baena, Francisco Cabello-Torres, Francisco Gracia, Cristina Lopez-Blau, M. Angela Nieto, Berta Sanchez-Laorden
bioRxiv 2022.11.23.517623; doi: https://doi.org/10.1101/2022.11.23.517623

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