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

Author

Listed:
  • Taghreed Hirz

    (Massachusetts General Hospital
    Harvard Stem Cell Institute
    Harvard University)

  • Shenglin Mei

    (Massachusetts General Hospital
    Harvard Medical School)

  • Hirak Sarkar

    (Harvard Medical School)

  • Youmna Kfoury

    (Massachusetts General Hospital
    Harvard Stem Cell Institute
    Harvard University)

  • Shulin Wu

    (Harvard Medical School
    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
    Broad Institute of Harvard and MIT)

  • 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
    Massachusetts General Hospital)

  • Chin-Lee Wu

    (Harvard Medical School
    Harvard Medical School)

  • David T. Scadden

    (Massachusetts General Hospital
    Harvard Stem Cell Institute
    Harvard University)

  • 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
    Harvard Medical School
    Broad Institute of Harvard and MIT
    Altos Labs)

  • David B. Sykes

    (Massachusetts General Hospital
    Harvard Stem Cell Institute
    Harvard University)

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.

Suggested Citation

  • 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 &, 2023. "Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36325-2
    DOI: 10.1038/s41467-023-36325-2
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