‘Science’ paper on the interaction between myeloid-derived suppressor cells and IDH-wild type glioblastomas
Haemopoietic stem cells give rise to myeloid and lymphoid lineages in the bone marrow. The myeloid lineage gives rise to immune cells that are ‘first responders’ - immune cells derived from myeloid lineage include neutrophils, monocytes (which could differentiate into macrophages and dendritic cells), basophils, eosinophils and mast cells.
In the paper by Jackson et al., from the University of Pennsylvania, they report on the possible role of another myeloid-derived immune cell, the myeloid-derived suppressor cells (MDSCs), in facilitating the growth of IDH-wild type glioblastoma.
These MDSCs usually act as immunomodulatory cells, inhibiting T-lymphocytes, dendritic cells, and natural killer cells, in order to prevent overreaction of the immune system.
There are several subtypes of MDSCs.
What Jackson C et al., found whilst several subtypes of MDSCs are in the microenvironment of glioblastomas, two subtypes: early myeloid-derived suppressor cells (E-MDSCs) and monocytic myeloid-derived suppressor cells (M-MDSC) are co-localised predominantly with IDH-wild type glioblastomas (more aggressive) GBM.
The IDH-wild-type glioblastomas appear to produce chemokines to attract E-MDSC cells; these E-MDSC in turn produce growth factors that promote tumour growth.
Few E-MDSCs were colocalised with IDH-mutant glioblastomas. It would appear that in IDH-mutant glioblastomas the genes that encode for chemokines that attract E-MDSCs are suppressed by hypermethylation.
Reference
Jackson C, Cherry C, Bom S, Dykema AG, Wang R, Thompson E, Zhang M, Li R, Ji Z, Hou W, Zhan W, Zhang H, Choi J, Vaghasia A, Hansen L, Wang W, Bergsneider B, Jones KM, Rodriguez F, Weingart J, Lucas CH, Powell J, Elisseeff J, Yegnasubramanian S, Lim M, Bettegowda C, Ji H, Pardoll D. Distinct myeloid-derived suppressor cell populations in human glioblastoma. Science. 2025 Jan 17;387(6731):eabm5214. doi: 10.1126/science.abm5214. Epub 2025 Jan 17. PMID: 39818911. [PubMed]
