Is there a causal link between PTEN deficient tumors and immunosuppressive tumor microenvironment?

Abstract

Abstract The PTEN tumor suppressor is the second most commonly inactivated gene across cancer types. While it’s role in PI3K/AKT and DNA damage pathways are clear, increasing evidences suggest that PTEN may also promote anti-tumor immunity. PTEN-deficient tumors are characterized by (i) reduced levels of cytotoxic T cells, helper T cells and NK cells, (ii) elevated pro-oncogenic inflammatory cytokines like CCL2 and (iii) increased levels of immunosuppressive cells such as MDSCs and Tregs. An intriguing possibility is that link between PTEN and anti-tumor immunity is mediated by the interferon signaling pathway. In this review, we summarize the evidences for the mechanistic link between PTEN deficiency and immunosuppressive tumor microenvironment and the interferon signaling pathway. We further discuss how the link between these pathways can be exploited for development of personalized immunotherapy for patients with PTEN deficient tumors.

Keywords

• PTEN
• Immunosuppressive tumor microenvironment
• Immunotherapy resistance
• Innate immunity
• Interferon
• cGAS/STING