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The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response

Checkpoint blockade therapies have changed the clinical management of metastatic melanoma patients considerably, showing survival benefits. Despite the clinical success, not all patients respond to treatment or they develop resistance. Although there are several treatment predictive biomarkers, unde...

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Autores principales: Cabrita, Rita, Mitra, Shamik, Sanna, Adriana, Ekedahl, Henrik, Lövgren, Kristina, Olsson, Håkan, Ingvar, Christian, Isaksson, Karolin, Lauss, Martin, Carneiro, Ana, Jönsson, Göran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140048/
https://www.ncbi.nlm.nih.gov/pubmed/32245160
http://dx.doi.org/10.3390/cancers12030742
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author Cabrita, Rita
Mitra, Shamik
Sanna, Adriana
Ekedahl, Henrik
Lövgren, Kristina
Olsson, Håkan
Ingvar, Christian
Isaksson, Karolin
Lauss, Martin
Carneiro, Ana
Jönsson, Göran
author_facet Cabrita, Rita
Mitra, Shamik
Sanna, Adriana
Ekedahl, Henrik
Lövgren, Kristina
Olsson, Håkan
Ingvar, Christian
Isaksson, Karolin
Lauss, Martin
Carneiro, Ana
Jönsson, Göran
author_sort Cabrita, Rita
collection PubMed
description Checkpoint blockade therapies have changed the clinical management of metastatic melanoma patients considerably, showing survival benefits. Despite the clinical success, not all patients respond to treatment or they develop resistance. Although there are several treatment predictive biomarkers, understanding therapy resistance and the mechanisms of tumor immune evasion is crucial to increase the frequency of patients benefiting from treatment. The PTEN gene is thought to promote immune evasion and is frequently mutated in cancer and melanoma. Another feature of melanoma tumors that may affect the capacity of escaping T-cell recognition is melanoma cell dedifferentiation characterized by decreased expression of the microphtalmia-associated transcription factor (MITF) gene. In this study, we have explored the role of PTEN in prognosis, therapy response, and immune escape in the context of MITF expression using immunostaining and genomic data from a large cohort of metastatic melanoma. We confirmed in our cohort that PTEN alterations promote immune evasion highlighted by decreased frequency of T-cell infiltration in such tumors, resulting in a worse patient survival. More importantly, our results suggest that dedifferentiated PTEN negative melanoma tumors have poor patient outcome, no T-cell infiltration, and transcriptional properties rendering them resistant to targeted- and immuno-therapy.
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spelling pubmed-71400482020-04-13 The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response Cabrita, Rita Mitra, Shamik Sanna, Adriana Ekedahl, Henrik Lövgren, Kristina Olsson, Håkan Ingvar, Christian Isaksson, Karolin Lauss, Martin Carneiro, Ana Jönsson, Göran Cancers (Basel) Article Checkpoint blockade therapies have changed the clinical management of metastatic melanoma patients considerably, showing survival benefits. Despite the clinical success, not all patients respond to treatment or they develop resistance. Although there are several treatment predictive biomarkers, understanding therapy resistance and the mechanisms of tumor immune evasion is crucial to increase the frequency of patients benefiting from treatment. The PTEN gene is thought to promote immune evasion and is frequently mutated in cancer and melanoma. Another feature of melanoma tumors that may affect the capacity of escaping T-cell recognition is melanoma cell dedifferentiation characterized by decreased expression of the microphtalmia-associated transcription factor (MITF) gene. In this study, we have explored the role of PTEN in prognosis, therapy response, and immune escape in the context of MITF expression using immunostaining and genomic data from a large cohort of metastatic melanoma. We confirmed in our cohort that PTEN alterations promote immune evasion highlighted by decreased frequency of T-cell infiltration in such tumors, resulting in a worse patient survival. More importantly, our results suggest that dedifferentiated PTEN negative melanoma tumors have poor patient outcome, no T-cell infiltration, and transcriptional properties rendering them resistant to targeted- and immuno-therapy. MDPI 2020-03-21 /pmc/articles/PMC7140048/ /pubmed/32245160 http://dx.doi.org/10.3390/cancers12030742 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cabrita, Rita
Mitra, Shamik
Sanna, Adriana
Ekedahl, Henrik
Lövgren, Kristina
Olsson, Håkan
Ingvar, Christian
Isaksson, Karolin
Lauss, Martin
Carneiro, Ana
Jönsson, Göran
The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response
title The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response
title_full The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response
title_fullStr The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response
title_full_unstemmed The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response
title_short The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response
title_sort role of pten loss in immune escape, melanoma prognosis and therapy response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140048/
https://www.ncbi.nlm.nih.gov/pubmed/32245160
http://dx.doi.org/10.3390/cancers12030742
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