Abstract:
Glioblastoma is a highly prevalent and aggressive form of primary brain tumor. It represents approximately 56% of all the
newly diagnosed gliomas. Macrophages are one of the major constituents of tumor-infltrating immune cells in the human
gliomas. The role of immunosuppressive macrophages is very well documented in correlation with the poor prognosis of
patients sufering from breast, prostate, bladder and cervical cancers. The current study highlights the correlation between the
tumor-associated macrophage phenotypes and glioma progression. We observed an increase in the pool of M2 macrophages
in high-grade gliomas, as confrmed by their CD68 and CD163 double-positive phenotype. In contrast, less M1 macrophages
were noticed in high-grade gliomas, as evidenced by the down-regulation in the expression of CCL3 marker. In addition,
we observed that higher gene expression ratio of CD163/CCL3 is associated with glioma progression. The Kaplan–Meier
survival plots indicate that glioma patients with lower expression of M2c marker (CD163), and higher expression of M1
marker (CCL3) had better survival. Furthermore, we examined the systemic immune response in the peripheral blood and
noted a predominance of M2 macrophages, myeloid-derived suppressor cells and PD-1+ CD4 T cells in glioma patients.
Thus, the study indicates a high gene expression ratio of CD163/CCL3 in high-grade gliomas as compared to low-grade
gliomas and signifcantly elevated frequency of M2 macrophages and PD-1+ CD4 T cells in the blood of tumor patients.
These parameters could be used as an indicator of the early diagnosis and prognosis of the disease.
