Related Experiment Video
Updated: Jan 11, 2026
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
PTEN deficiency impairs IL-15-dependent T-cell immunity against prostate cancer
Yujie Xing1, Zixuan Zeng1, Chi Wang1
1Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Abstract:
Prostate cancer (PCa) is widely recognized as an immunologically "cold" tumor that responds poorly to immunotherapy, largely due to its poorly infiltrated immune microenvironment. Genetic loss or functional inactivation of phosphatase and tensin homolog (PTEN) is a well-established driver of PCa tumorigenesis and progression. However, the mechanisms by which PTEN-deficiency shapes the tumor immune landscape, particularly T cell infiltration and activity, remain poorly understood. Here, we report that PTEN deficiency is associated with reduced T-cell infiltration in human PCa tissues. CRISPR/Cas9-mediated knockout (KO) of Pten in murine syngeneic tumor models similarly results in diminished intratumoral CD8+ T cell accumulation. Mechanistically, loss of PTEN suppresses IL-15 production by impairing activation of the cGAS-STING signaling pathway. Restoration of IL-15 in Pten KO PCa cells reinvigorates antitumor immunity and promotes T-cell infiltration within the tumor microenvironment. Together, our findings identify PTEN as a critical regulator of IL-15-associated T-cell immunity and suggest that IL-15-based therapeutic strategies may offer a promising approach for PTEN-deficient PCa.
Insights
Phosphatase and tensin homolog (PTEN) loss in prostate cancer reduces T-cell infiltration by suppressing IL-15. Restoring IL-15 boosts antitumor immunity, suggesting IL-15 therapies for PTEN-deficient prostate cancer.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Prostate cancer (PCa) is often immunologically "cold", limiting immunotherapy effectiveness due to poor immune cell infiltration.
- Loss of phosphatase and tensin homolog (PTEN) is a key driver of PCa development and progression.
- The impact of PTEN deficiency on the tumor immune microenvironment, especially T-cell activity, is not well understood.
Purpose of the Study:
- To investigate how PTEN deficiency influences T-cell infiltration and antitumor immunity in prostate cancer.
- To elucidate the molecular mechanisms linking PTEN loss to immune evasion in PCa.
- To explore the therapeutic potential of IL-15 in PTEN-deficient PCa.
Main Methods:
- Analysis of PTEN deficiency and T-cell infiltration in human PCa tissues.
- CRISPR/Cas9-mediated Pten knockout in murine syngeneic tumor models.
- Assessment of IL-15 production and cGAS-STING pathway activation.
- Evaluation of IL-15 restoration effects on T-cell infiltration and antitumor immunity.
Main Results:
- PTEN deficiency correlates with reduced T-cell infiltration in human PCa.
- Pten knockout in mouse models leads to decreased intratumoral CD8+ T-cell accumulation.
- PTEN loss suppresses IL-15 production via impaired cGAS-STING signaling.
- Restoring IL-15 in Pten-deficient PCa cells enhances T-cell infiltration and antitumor responses.
Conclusions:
- PTEN is a critical regulator of IL-15-mediated T-cell immunity in prostate cancer.
- PTEN deficiency impairs antitumor immunity by suppressing IL-15 production.
- IL-15-based therapies show promise for treating PTEN-deficient prostate cancer.
Related Concept Videos
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:27Tumor Immunotherapy