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

Nat Commun. 2022 Feb 9;13(1):767. doi: 10.1038/s41467-022-28372-y.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain Neoplasms / immunology
  • Female
  • Glioma / immunology
  • Humans
  • Immunotherapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells
  • Prognosis
  • S100 Calcium-Binding Protein A4 / genetics
  • S100 Calcium-Binding Protein A4 / isolation & purification*
  • Single-Cell Analysis / methods*
  • Tumor Microenvironment / immunology


  • S100 Calcium-Binding Protein A4
  • S100A4 protein, human