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

Author(s)

Vidotto, Thiago ^[1] ; Melo, Camila Morais ^[1] ; Castelli, Erick ^[2] ; Koti, Madhuri ^{[3, 4]} ; dos Reis, Rodolfo Borges ^[5] ; Squire, Jeremy A. ^{[6, 1]}

Affiliation

^[1] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Genet, Ribeirao Preto - Brazil

^[2] Univ Estadual Paulista, Med Sch Botucatu, Dept Pathol, Botucatu, SP - Brazil

^[3] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON - Canada

^[4] Queens Univ, Queens Canc Res Inst, Canc Biol & Genet, Kingston, ON - Canada

^[5] Clin Hosp Ribeirao Preto, Ribeirao Preto - Brazil

^[6] Queens Univ, Dept Pathol & Mol Med, Kingston, ON - Canada

• Document type: Review article
• Source: BRITISH JOURNAL OF CANCER; v. 122, n. 12 APR 2020.
• Web of Science Citations: 1

Abstract

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. (AU)

• FAPESP's process: 15/09111-5 - Investigation of Clinically Useful Genomic Biomarkers in Prostate Cancer
• Grantee: Jeremy Andrew Squire
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/08614-9 - The Role Of PTEN in STAT1 And STAT3 Mediated Inflammatory Response in Prostate Cancer
• Grantee: Thiago Vidotto
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 15/22785-5 - The Role of PTEN Gene Loss in Facilitating the Inflammatory Response in Prostate Cancer
• Grantee: Thiago Vidotto
• Support Opportunities: Scholarships in Brazil - Doctorate