Document Type

Article

Publication Date

2-9-2022

Publication Title

Nat Commun

Keywords

JGM

JAX Source

Nat Commun 2022 Feb 9; 13(1):767

Volume

13

Issue

1

First Page

767

Last Page

767

ISSN

2041-1723

PMID

35140215

DOI

https://doi.org/10.1038/s41467-022-28372-y

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.

Comments

We thank Tetsuo Ashizawa, Dorothy Lewis, Brandi Mattson, and Taneli Helenius for
their editorial and Matthew G. Landry for graphic design assistance.

Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License.

Share

COinS