Dataset Information

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

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.

SUBMITTER: Abdelfattah N

PROVIDER: S-EPMC8828877 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Abdelfattah Nourhan N Kumar Parveen P Wang Caiyi C Leu Jia-Shiun JS Flynn William F WF Gao Ruli R Baskin David S DS Pichumani Kumar K Ijare Omkar B OB Wood Stephanie L SL Powell Suzanne Z SZ Haviland David L DL Parker Kerrigan Brittany C BC Lang Frederick F FF Prabhu Sujit S SS Huntoon Kristin M KM Jiang Wen W Kim Betty Y S BYS George Joshy J Yun Kyuson K

Nature communications 20220209 1

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 wh ...[more]

PMID: 35140215

Similar Datasets

Project description:BackgroundPulmonary arterial hypertension (PAH) is a critical cardiopulmonary vascular disorder marked by the progressive elevation of pulmonary artery pressure, increased pulmonary vascular resistance, and eventual right heart failure. Research has shown that various immune cells play a significant role in the pathogenesis of PAH, both in patients diagnosed with the condition and in experimental models of PAH. Cell-cell communication is important for PAH progression and therapies, while the global cell landscape of intercellular signaling has not been elucidated.MethodsWe performed single-cell RNA sequencing on NCBI Gene Expression Omnibus (GEO) databases GSE169471, GSE 210248, GSE228643 and GSE244781, and analyzed lung tissue samples across healthy controls and PAH patients. In total, approximately 124,561 cells were analyzed and a total 34 clusters were identified. We integrated the sequencing results of multiple samples and used an enhanced single-cell sequencing workflow to overcome the limitations of a single study.ResultsIn this study, we elucidated the functional characteristics and potential regulatory interactions of several cell subpopulations that have not been previously documented in similar research. We constructed a comprehensive landscape of cell communications at the single-cell resolution, which is expected to significantly advance the development of personalized diagnostic and therapeutic strategies for PAH. We demonstrated the transcriptomic features of different cell types in PAH patients. We presented an in-depth analysis of T cell subsets, myeloid cell heterogeneity and a comprehensive analysis of SMCs and FBs subsets in PAH. T cell heterogeneity and functional dynamics were exhibited in PAH, which suggests that targeting cytotoxic regulation may be a potential therapeutic strategy. Significant changes and potential functions of myeloid cell subsets in PAH patients and we especially focused on GPNMB+ macrophages. In addition, CellChat and NicheNet analyses reveal altered intercellular communication and dys-regulated signaling pathways in PAH progression. The enhanced MIF and IL-1 signaling suggests that the induced inflammatory response in PAH is greatly driven.ConclusionsWe systematically explored the immune heterogeneity and population and target cells in PAH, which may be valuable for developing new and precise therapies.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets