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

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. Haviland, Brittany C. Parker Kerrigan, Frederick F. Lang, Sujit S. Prabhu, Kristin M. Huntoon, Wen Jiang, Betty Y. S. Kim, Joshy George and Kyuson Yun ()
Additional contact information
Nourhan Abdelfattah: Houston Methodist Research Institute
Parveen Kumar: The Jackson Laboratory for Genomic Medicine
Caiyi Wang: Houston Methodist Research Institute
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
Kumar Pichumani: Houston Methodist Neurological Institute
Omkar B. Ijare: Houston Methodist Neurological Institute
Stephanie L. Wood: Houston Methodist Neurological Institute
Suzanne Z. Powell: Houston Methodist Neurological Institute
David L. Haviland: Houston Methodist Research Institute
Brittany C. Parker Kerrigan: The University of Texas MD Anderson Cancer Center
Frederick F. Lang: 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
Wen Jiang: The University of Texas MD Anderson Cancer Center
Betty Y. S. Kim: The University of Texas MD Anderson Cancer Center
Joshy George: The Jackson Laboratory for Genomic Medicine
Kyuson Yun: Houston Methodist Research Institute

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28372-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28372-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28372-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().