Abstract
Glioblastoma (GBM) is the most aggressive tumor in the central nervous system and contains a highly immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages and microglia (TAMs) are a dominant population of immune cells in the GBM TME that contribute to most GBM hallmarks, including immunosuppression. The understanding of TAMs in GBM has been limited by the lack of powerful tools to characterize them. However, recent progress on single-cell technologies offers an opportunity to precisely characterize TAMs at the single-cell level and identify new TAM subpopulations with specific tumor-modulatory functions in GBM. In this Review, we discuss TAM heterogeneity and plasticity in the TME and summarize current TAM-targeted therapeutic potential in GBM. We anticipate that the use of single-cell technologies followed by functional studies will accelerate the development of novel and effective TAM-targeted therapeutics for GBM patients.
| Original language | English (US) |
|---|---|
| Article number | e163446 |
| Journal | Journal of Clinical Investigation |
| Volume | 133 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 3 2023 |
Funding
Authorship note: FK and LP contributed equally to this work. Conflict of interest: ABH serves on the advisory board of Caris Life Sciences and the WCG Oncology Advisory Board; receives royalty and milestone payments from DNA-trix for the licensing of “Biomarkers and combination therapies using oncolytic virus and immunomodulation” (patent 11,065,285); and is supported by research grants from Celularity, Codiak BioSciences, and AbbVie. She additionally has active granted patents for “miRNA for treating cancer and for use with adoptive immunotherapies” (patent 9,675,633) and “Concurrent chemotherapy and immunotherapy” (patent 9,399,662), with a patent pending for “Low intensity ultrasound combination cancer therapies” (international application PCT/US2022/019435 and US 63/158,642). Copyright: © 2023, Khan et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. Reference information: J Clin Invest. 2023;133(1):e163446. https://doi.org/10.1172/JCI163446. This work was supported by NIH R00 CA240896, NIH R01 NS124594, Department of Defense Career Development Award W81XWH-21-1-0380, NIH P50 CA221747, Cancer Research Foundation Young Investigator Award, Lynn Sage Scholar Award, American Cancer Society Institutional Research Grant IRG-21-144-27, philanthropic donation from Mindy Jacobson and the Bill Bass Foundation, Northwestern University start-up funds, and the Robert H. Lurie Comprehensive Cancer Center.
ASJC Scopus subject areas
- General Medicine