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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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/3/742 |
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| author | Rita Cabrita Shamik Mitra Adriana Sanna Henrik Ekedahl Kristina Lövgren Håkan Olsson Christian Ingvar Karolin Isaksson Martin Lauss Ana Carneiro Göran Jönsson |
| author_facet | Rita Cabrita Shamik Mitra Adriana Sanna Henrik Ekedahl Kristina Lövgren Håkan Olsson Christian Ingvar Karolin Isaksson Martin Lauss Ana Carneiro Göran Jönsson |
| author_sort | Rita Cabrita |
| collection | DOAJ |
| 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 <i>PTEN</i> 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 (<i>MITF</i>) gene. In this study, we have explored the role of PTEN in prognosis, therapy response, and immune escape in the context of <i>MITF</i> 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. |
| first_indexed | 2024-03-12T09:22:03Z |
| format | Article |
| id | doaj.art-45432b96ae1a445daabefd14e10568c3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T09:22:03Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-45432b96ae1a445daabefd14e10568c32023-09-02T14:25:55ZengMDPI AGCancers2072-66942020-03-0112374210.3390/cancers12030742cancers12030742The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy ResponseRita Cabrita0Shamik Mitra1Adriana Sanna2Henrik Ekedahl3Kristina Lövgren4Håkan Olsson5Christian Ingvar6Karolin Isaksson7Martin Lauss8Ana Carneiro9Göran Jönsson10Division of Oncology, Department of Clinical Sciences, Lund University, 22381 Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund University, 22381 Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund University, 22381 Lund, SwedenDepartment of Oncology, Skåne University Hospital, 22185 Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund University, 22381 Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund University, 22381 Lund, SwedenDepartment of Surgery, Skåne University Hospital, 22185 Lund, SwedenDepartment of Surgery, Department of Clinical Sciences, Lund University, 22185 Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund University, 22381 Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund University, 22381 Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund University, 22381 Lund, SwedenCheckpoint 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 <i>PTEN</i> 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 (<i>MITF</i>) gene. In this study, we have explored the role of PTEN in prognosis, therapy response, and immune escape in the context of <i>MITF</i> 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.https://www.mdpi.com/2072-6694/12/3/742melanomaptenimmune evasion |
| spellingShingle | Rita Cabrita Shamik Mitra Adriana Sanna Henrik Ekedahl Kristina Lövgren Håkan Olsson Christian Ingvar Karolin Isaksson Martin Lauss Ana Carneiro Göran Jönsson The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response Cancers melanoma pten immune evasion |
| 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 | melanoma pten immune evasion |
| url | https://www.mdpi.com/2072-6694/12/3/742 |
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