Figure 3. Model of aberrant granulocyte differentiation in mIDH1 tumors.

(A) In WT IDH1 tumors, tumor cells express low levels of G-CSF and the TME contains a high number of immunosuppressive MDSCs. (B) Through epigenetic reprogramming mediated by mIDH1-induced 2-HG accumulation, mIDH1 glioma cells express and secrete G-CSF. Circulating G-CSF has a direct effect on hematopoiesis in the bone marrow and spleen, promoting the expansion, differentiation, and mobilization of granulocytic myeloid cells. As a result, the granulocytes recruited to the TME are mainly neutrophils and preneutrophils, with inhibitory PMN-MDSCs, constituting a smaller fraction of the total granulocytes in the mIDH1 tumor. Figure adapted from Alghamri et al. (63).