Predominance of M2 macrophages in gliomas leads to the suppression of local and systemic immunity.
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-infiltrating immune cells in the human gliomas. The role of immunosuppressive macrophages is very well documented in correlation with the poor prognosis of patients suffering 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 confirmed 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 significantly 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.
['Vidyarthi|Aurobind|A|', 'Agnihotri|Tapan|T|', 'Khan|Nargis|N|', 'Singh|Sanpreet|S|', 'Tewari|Manoj K|MK|', 'Radotra|Bishan D|BD|', 'Chatterjee|Deepyan|D|', 'Agrewala|Javed N|JN|']
D015703:Antigens, CD D015214:Antigens, Differentiation, Myelomonocytic D001932:Brain Neoplasms D015496:CD4-Positive T-Lymphocytes D063646:Carcinogenesis D054405:Chemokine CCL3 D016207:Cytokines D018450:Disease Progression D015972:Gene Expression Regulation, Neoplastic D005909:Glioblastoma D006801:Humans D007108:Immune Tolerance D056724:Immunity, Humoral D008264:Macrophages D000072737:Myeloid-Derived Suppressor Cells D061026:Programmed Cell Death 1 Receptor D011956:Receptors, Cell Surface D016019:Survival Analysis D018418:Th2 Cells
Glioma Tumor-associated macrophages CD163 CCL3 PD-1