Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses
Taghreed Hirz, Shenglin Mei, Hirak Sarkar, Youmna Kfoury, Shulin Wu, Bronte Manouk Verhoeven, Alexander O. Subtelny, Dimitar V. Zlatev, Matthew W. Wszolek, Keyan Salari, Evan Murray, Fei Chen, Evan Z. Macosko, Chin‐Lee Wu, David T. Scadden, Douglas M. Dahl, Ninib Baryawno, Philip J. Saylor, Peter V. Kharchenko, David B. Sykes
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.