Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses

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.

Automated summary

The treatment of low-risk primary prostate cancer only requires active surveillance, while high-risk disease necessitates multimodal treatment including surgery, radiation therapy, and hormonal therapy. Recurrence and metastatic disease development remain clinical challenges due to immune escape and tumor progression mechanisms that are not well understood. Through single-cell RNA sequencing and spatial transcriptomic analyses, we comprehensively describe the tumor microenvironment in localized prostate cancer and its differences compared to adjacent normal samples and healthy controls. Our study reveals an immune suppressive tumor microenvironment characterized by suppressive myeloid populations, exhausted T-cells, and high stromal angiogenic activity. We also infer cell-to-cell relationships within undissociated tissue sections using ligand-receptor interaction measurements. Overall, our work provides a highly detailed and comprehensive resource on the prostate tumor microenvironment and tumor-stromal cell interactions.