PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Cancer immunotherapy aims to re-engineer the host immune system towards an anti-tumor state, showing significant clinical efficacy in various cancers.
• Despite advancements, many immunotherapies face clinical failure, often attributed to a lack of reliable prognostic and predictive biomarkers.
• The tumor suppressor gene, phosphatase and tensin homolog on chromosome 10 (PTEN), is increasingly recognized for its role in modulating the tumor microenvironment (TME) and influencing immunotherapy outcomes.

Purpose of the Study:

• To review the current understanding of PTEN's diverse functions within different tumor microenvironment compartments.
• To elucidate how PTEN influences immune and stromal cells, thereby affecting sensitivity or resistance to immunotherapy.
• To discuss the potential of PTEN as a biomarker for predicting clinical response to cancer immunotherapy.

Main Methods:

• Literature review of preclinical and clinical studies.
• Analysis of PTEN's role in immune cell function within the TME.
• Examination of PTEN's impact on stromal cell components of the TME.
• Synthesis of data on PTEN's modulation of resistance and sensitivity to various immunotherapies.

Main Results:

• PTEN plays a critical role in shaping the TME, impacting both immune and stromal cell populations.
• Altered PTEN status influences the efficacy of different immunotherapeutic strategies.
• PTEN's function within the TME is a key determinant of patient response to immunotherapy.

Conclusions:

• PTEN is a crucial regulator of the tumor microenvironment and immunotherapy response.
• Understanding PTEN's multifaceted roles is essential for developing more effective cancer immunotherapies.
• PTEN holds significant potential as a predictive biomarker for cancer immunotherapy outcomes.