Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses
Year: 2023
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Authors: Taghreed Hirz, Shenglin Mei, Hirak Sarkar, Youmna Kfoury, Shulin Wu, Bronte M. 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
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: Prostate Cancer Foundation, Andrew and Jaime Sullivan Family Foundation, Cancerfonden, National Institutes of Health, Harvard Stem Cell Institute, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, H2020 European Research Council
Awards: Sequence-specific Hybridization Capture for Discovery of Proteoform–lncRNA Interactions in Prostate Cancer, Cell and Molecular Dynamics of Hematopoiesis In Vivo, G6265702644, Stromal Regulation of Bone Metastasis, Statistical methods for analysis of single-cell variability, Using cell-cell interactions to unlock new cancer treatments: Forcing neural crest tumors back onto the developmental path, Dana-Farber/Harvard Cancer Center
OpenAlex ID: W4319440743