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

Cabrita, Rita LU ; Mitra, Shamik LU ; Sanna, Adriana LU ; Ekedahl, Henrik LU ; Lövgren, Kristina LU ; Olsson, Håkan LU ; Ingvar, Christian LU ; Isaksson, Karolin LU ; Lauss, Martin LU and Carneiro, Ana LU , et al. (2020) In Cancers 12(3).
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancers
volume
12
issue
3
article number
742
publisher
Multidisciplinary Digital Publishing Institute (MDPI)
external identifiers
  • scopus:85082929160
  • pmid:32245160
ISSN
2072-6694
DOI
10.3390/cancers12030742
language
English
LU publication?
yes
id
fc3dfbc2-5632-4b4f-a2ea-92a01a17b3ce
date added to LUP
2020-03-26 16:44:52
date last changed
2020-12-29 03:31:01
@article{fc3dfbc2-5632-4b4f-a2ea-92a01a17b3ce,
  abstract     = {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.},
  author       = {Cabrita, Rita and Mitra, Shamik and Sanna, Adriana and Ekedahl, Henrik and Lövgren, Kristina and Olsson, Håkan and Ingvar, Christian and Isaksson, Karolin and Lauss, Martin and Carneiro, Ana and Jönsson, Göran},
  issn         = {2072-6694},
  language     = {eng},
  month        = {03},
  number       = {3},
  publisher    = {Multidisciplinary Digital Publishing Institute (MDPI)},
  series       = {Cancers},
  title        = {The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response},
  url          = {http://dx.doi.org/10.3390/cancers12030742},
  doi          = {10.3390/cancers12030742},
  volume       = {12},
  year         = {2020},
}