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Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target

Author

Listed:
  • Nourhan Abdelfattah

    (Houston Methodist Research Institute)

  • Parveen Kumar

    (The Jackson Laboratory for Genomic Medicine)

  • Caiyi Wang

    (Houston Methodist Research Institute
    Central South University)

  • Jia-Shiun Leu

    (Houston Methodist Research Institute)

  • William F. Flynn

    (The Jackson Laboratory for Genomic Medicine)

  • Ruli Gao

    (Center for Bioinformatics and Computational Biology. Houston Methodist Research Institute Houston)

  • David S. Baskin

    (Houston Methodist Neurological Institute
    Houston Methodist Neurological Institute
    Weill Cornell Medical College)

  • Kumar Pichumani

    (Houston Methodist Neurological Institute
    Houston Methodist Neurological Institute
    Weill Cornell Medical College)

  • Omkar B. Ijare

    (Houston Methodist Neurological Institute
    Houston Methodist Neurological Institute)

  • Stephanie L. Wood

    (Houston Methodist Neurological Institute)

  • Suzanne Z. Powell

    (Houston Methodist Neurological Institute
    Weill Cornell Medical College
    Houston Methodist Hospital
    Weill Cornell Medical College)

  • David L. Haviland

    (Houston Methodist Research Institute)

  • Brittany C. Parker Kerrigan

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Frederick F. Lang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Sujit S. Prabhu

    (The University of Texas MD Anderson Cancer Center)

  • Kristin M. Huntoon

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Wen Jiang

    (The University of Texas MD Anderson Cancer Center)

  • Betty Y. S. Kim

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Joshy George

    (The Jackson Laboratory for Genomic Medicine)

  • Kyuson Yun

    (Houston Methodist Research Institute
    Weill Cornell Medical College)

Abstract

A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and the molecular heterogeneity of immune infiltrates in gliomas. Here, we report an integrated analysis of 201,986 human glioma, immune, and other stromal cells at the single cell level. In doing so, we discover extensive spatial and molecular heterogeneity in immune infiltrates. We identify molecular signatures for nine distinct myeloid cell subtypes, of which five are independent prognostic indicators of glioma patient survival. Furthermore, we identify S100A4 as a regulator of immune suppressive T and myeloid cells in GBM and demonstrate that deleting S100a4 in non-cancer cells is sufficient to reprogram the immune landscape and significantly improve survival. This study provides insights into spatial, molecular, and functional heterogeneity of glioma and glioma-associated immune cells and demonstrates the utility of this dataset for discovering therapeutic targets for this poorly immunogenic cancer.

Suggested Citation

  • Nourhan Abdelfattah & Parveen Kumar & Caiyi Wang & Jia-Shiun Leu & William F. Flynn & Ruli Gao & David S. Baskin & Kumar Pichumani & Omkar B. Ijare & Stephanie L. Wood & Suzanne Z. Powell & David L. H, 2022. "Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28372-y
    DOI: 10.1038/s41467-022-28372-y
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    Cited by:

    1. Frank A. Giordano & Julian P. Layer & Sonia Leonardelli & Lea L. Friker & Roberta Turiello & Dillon Corvino & Thomas Zeyen & Christina Schaub & Wolf Müller & Elena Sperk & Leonard Christopher Schmeel , 2024. "L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Crismita Dmello & Junfei Zhao & Li Chen & Andrew Gould & Brandyn Castro & Victor A. Arrieta & Daniel Y. Zhang & Kwang-Soo Kim & Deepak Kanojia & Peng Zhang & Jason Miska & Ragini Yeeravalli & Karl Hab, 2023. "Checkpoint kinase 1/2 inhibition potentiates anti-tumoral immune response and sensitizes gliomas to immune checkpoint blockade," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Ki Oh & Yun Jae Yoo & Luke A. Torre-Healy & Manisha Rao & Danielle Fassler & Pei Wang & Michael Caponegro & Mei Gao & Joseph Kim & Aaron Sasson & Georgios Georgakis & Scott Powers & Richard A. Moffitt, 2023. "Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Fatima Khan & Yiyun Lin & Heba Ali & Lizhi Pang & Madeline Dunterman & Wen-Hao Hsu & Katie Frenis & R. Grant Rowe & Derek A. Wainwright & Kathleen McCortney & Leah K. Billingham & Jason Miska & Craig , 2024. "Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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