Related Experiment Video
Updated: Aug 11, 2025
Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial
Taghreed Hirz1,2,3, Shenglin Mei4,5, Hirak Sarkar6
1Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA. THIRZ@mgh.harvard.edu.
Abstract:
The treatment of low-risk primary prostate cancer entails active surveillance only, while high-risk disease requires multimodal treatment including surgery, radiation therapy, and hormonal therapy. Recurrence and development of metastatic disease remains a clinical problem, without a clear understanding of what drives immune escape and tumor progression. Here, we comprehensively describe the tumor microenvironment of localized prostate cancer in comparison with adjacent normal samples and healthy controls. Single-cell RNA sequencing and high-resolution spatial transcriptomic analyses reveal tumor context dependent changes in gene expression. Our data indicate that an immune suppressive tumor microenvironment associates with suppressive myeloid populations and exhausted T-cells, in addition to high stromal angiogenic activity. We infer cell-to-cell relationships from high throughput ligand-receptor interaction measurements within undissociated tissue sections. Our work thus provides a highly detailed and comprehensive resource of the prostate tumor microenvironment as well as tumor-stromal cell interactions.
Insights
This study details the prostate tumor microenvironment, revealing immune suppressive cells and high angiogenic activity in high-risk prostate cancer. Understanding these factors is crucial for developing new treatments to prevent disease recurrence and metastasis.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Prostate cancer recurrence and metastasis are significant clinical challenges.
- The underlying mechanisms driving immune escape and tumor progression remain poorly understood.
- Effective treatment strategies for high-risk prostate cancer require a deeper insight into the tumor microenvironment.
Purpose of the Study:
- To comprehensively characterize the tumor microenvironment (TME) in localized prostate cancer.
- To compare the TME of prostate tumors with adjacent normal tissues and healthy controls.
- To identify key cellular and molecular components contributing to immune suppression and tumor progression.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) for gene expression analysis.
- High-resolution spatial transcriptomics to map cellular architecture.
- Ligand-receptor interaction analysis to infer cell-to-cell communication.
Main Results:
- Identified an immune-suppressive TME associated with suppressive myeloid cells and exhausted T-cells.
- Observed high stromal angiogenic activity within the tumor microenvironment.
- Revealed tumor context-dependent alterations in gene expression and cell-cell interactions.
Conclusions:
- The prostate tumor microenvironment exhibits distinct immune-suppressive characteristics.
- Stromal angiogenic activity and specific immune cell populations contribute to tumor progression.
- This study provides a detailed resource for understanding prostate cancer TME and cell interactions, aiding future therapeutic development.
