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Investigating the effects of PTEN mutations on cGAS-STING pathway in glioblastoma tumours

Eda Dogan1, Zafer Yildirim1, Taner Akalin2

  • 1Department of Medical Biology, Ege University Faculty of Medicine, Izmir, Türkiye.

Journal of Neuro-Oncology
|January 12, 2024
PubMed
Abstract

Insights

PTEN loss in glioblastoma tumors suppresses immune responses through the cGAS-STING pathway. This finding highlights the importance of assessing PTEN status for effective glioblastoma immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • PTEN is a tumor suppressor gene frequently mutated in cancers.
  • PTEN loss impacts tumor microenvironment and immunogenicity.
  • The cGAS-STING pathway is crucial for inflammation and immune response.

Purpose of the Study:

  • To investigate the relationship between PTEN status and cGAS-STING pathway activity.
  • To evaluate the impact of PTEN loss on glioblastoma immunogenicity.
  • To explore PTEN's role in the tumor microenvironment of glioblastoma.

Main Methods:

  • Sequencing and analysis of PTEN coding regions in 36 glioblastoma samples.
  • Evaluation of PTEN expression using qRT-PCR, Western blot, and immunohistochemistry.
  • Assessment of cGAS-STING activity via interferon-stimulated gene expression, cGAMP levels, CD8 infiltration, and Granzyme B.

Main Results:

  • Mutant PTEN correlated with significantly lower PTEN mRNA and protein expression.
  • PTEN loss was associated with reduced STING, IRF3, NF-KB1, and RELA mRNA levels.
  • PTEN loss led to decreased IFNB, IFIT2, CD8 infiltration, cGAMP, and Granzyme B levels.

Conclusions:

  • PTEN loss induces immunosuppression in glioblastoma via the cGAS-STING pathway.
  • PTEN status is a critical factor for glioblastoma patients, especially when considering immunotherapy.
  • Targeting PTEN or the cGAS-STING pathway may enhance immunotherapeutic efficacy in glioblastoma.
Keywords:
GlioblastomaImmunogenicityInterferon responsePTENcGAS-STING pathway

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