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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7140048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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