Emerging role of PTEN loss in evasion of the immune response to tumours

Mutations in PTEN activate the phosphoinositide 3-kinase (PI3K) signalling network, leading to many of the characteristic phenotypic changes of cancer. However, the primary effects of this gene on oncogenesis through control of the PI3K–AKT–mammalian target of rapamycin (mTOR) pathway might not be t...

Full description

Saved in:
Bibliographic Details
Published in:British journal of cancer 2020-06, Vol.122 (12), p.1732-1743
Main Authors: Vidotto, Thiago, Melo, Camila Morais, Castelli, Erick, Koti, Madhuri, dos Reis, Rodolfo Borges, Squire, Jeremy A.
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
631/208/69
631/67/327
692/4028/67/1244
692/53/2422
AKT protein
Animals
Biomarkers, Tumor - genetics
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer Research
Clinical trials
DNA damage
DNA repair
Drug Resistance
Epidemiology
Genomics
Humans
Immune checkpoint
Immunotherapy
Interferon
Kinases
Lymphocytes T
Molecular Medicine
Mutation
Neoplasms - genetics
Neoplasms - immunology
Oncology
PTEN Phosphohydrolase - genetics
PTEN Phosphohydrolase - immunology
PTEN protein
Rapamycin
Review
Review Article
Signal transduction
TOR protein
Tumorigenesis
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mutations in PTEN activate the phosphoinositide 3-kinase (PI3K) signalling network, leading to many of the characteristic phenotypic changes of cancer. However, the primary effects of this gene on oncogenesis through control of the PI3K–AKT–mammalian target of rapamycin (mTOR) pathway might not be the only avenue by which PTEN affects tumour progression. PTEN has been shown to regulate the antiviral interferon network and thus alter how cancer cells communicate with and are targeted by immune cells. An active, T cell-infiltrated microenvironment is critical for immunotherapy success, which is also influenced by mutations in DNA damage repair pathways and the overall mutational burden of the tumour. As PTEN has a role in the maintenance of genomic integrity, it is likely that a loss of PTEN affects the immune response at two different levels and might therefore be instrumental in mediating failed responses to immunotherapy. In this review, we summarise findings that demonstrate how the loss of PTEN function elicits specific changes in the immune response in several types of cancer. We also discuss ongoing clinical trials that illustrate the potential utility of PTEN as a predictive biomarker for immune checkpoint blockade therapies.
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-020-0834-6