Article Text

Download PDFPDF

1040-D Identification of four clinically-relevant immunomodulatory programs shared across nearly all glioma-associated myeloid cells
  1. Tyler E Miller1,
  2. Chadi El Farran2,
  3. Charles Couturier3,
  4. Zeyu Chen2,
  5. Joshua D’Antonio2,
  6. Alex Shalek4,
  7. Kevin Petrecca5,
  8. Mario Suva1 and
  9. Bradley Bernstein2
  1. 1Massachusetts General Hospital, Boston, MA, USA
  2. 2Dana Farber Cancer Institute, Boston, MA, USA
  3. 3Broad Institute of MIT and Harvard, Cambridge, MA, USA
  4. 4Massachusetts Institute of Technology, Cambridge, MA, USA
  5. 5McGill University, Montreal, QC, Canada
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Gliomas are incurable malignancies notable for an immunosuppressive microenvironment with abundant myeloid cells whose immunomodulatory properties remain poorly defined.

Methods We utilize scRNA-seq data for 183,062 myeloid cells from 85 human tumors and integrate mitochondrial DNA-based lineage tracing, spatial transcriptomics, and functional organoid models.

Results We discover that nearly all glioma-associated myeloid cells express at least one of four immunomodulatory activity programs. These include a Scavenger Immunosuppressive program, a C1Q Immunosuppressive program, a CXCR4 Inflammatory program, and an IL1B inflammatory program. We reveal that these programs are driven by microenvironmental cues and therapies rather than myeloid cell type or origin. All four programs are present in lower-grade and high-grade gliomas and expressed in multiple myeloid cell types derived from blood or resident myeloid cell origins. The Scavenger Immunosuppressive program is induced in hypoxic regions, while the C1Q Immunosuppressive program is driven by dexamethasone. Both immunosuppressive programs are less prevalent in lower-grade gliomas, which are instead enriched for the CXCR4 Inflammatory program. We validated this striking myeloid cell plasticity by demonstrating that application of peripheral blood monocytes to glioma organoid models leads to de novo induction of microglia, macrophage and dendritic cell identities, and all four immunomodulatory programs.

Conclusions Our study provides a resource and new framework to understand immunomodulatory myeloid cells in glioma, and a foundation to develop effective immunotherapy strategies for glioma patients.

Ethics Approval All work with human subjects was approved by the Dana Farber Cancer Institute’s Institutional Review Board under the protocol 10-417.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.