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 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 and David B. Sykes ()
Additional contact information
Taghreed Hirz: Massachusetts General Hospital
Shenglin Mei: Massachusetts General Hospital
Hirak Sarkar: Harvard Medical School
Youmna Kfoury: Massachusetts General Hospital
Shulin Wu: Harvard Medical School
Bronte M. Verhoeven: Department of Women’s and Children’s Health, Karolinska Institutet
Alexander O. Subtelny: Harvard Medical School
Dimitar V. Zlatev: Harvard Medical School
Matthew W. Wszolek: Harvard Medical School
Keyan Salari: Harvard Medical School
Evan Murray: Broad Institute of Harvard and MIT
Fei Chen: Broad Institute of Harvard and MIT
Evan Z. Macosko: Broad Institute of Harvard and MIT
Chin-Lee Wu: Harvard Medical School
David T. Scadden: Massachusetts General Hospital
Douglas M. Dahl: Harvard Medical School
Ninib Baryawno: Department of Women’s and Children’s Health, Karolinska Institutet
Philip J. Saylor: Harvard Medical School
Peter V. Kharchenko: Harvard Stem Cell Institute
David B. Sykes: Massachusetts General Hospital

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36325-2

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