M2 macrophages in glioma associated with local and systemic immunosuppression in patients

Backgroundglioblastoma (GBM) is the most common and malignant primary brain tumor in the central nervous system, accounting for 56% of all gliomasThe immunosuppression caused by glioma cells is one of the main reasons for poor prognosis and short survival in glioma patientsMacrophages are natural immune cells found in most tumor microenvironments; Tumor-related macrophages (tumor-associated macrophages, TAMs) are the M2 subtype macrophages phenotypes phenotypes that promote tumorsStudies have shown that suppressed immune cells interact with glioma cells to promote tumor progressionThe effect syme of immunosuppressive macrophages is associated with poor prognosis in patients with breast cancer, prostate cancer, bladder cancer and cervical cancer, and studies have shown that glioma can induce systemic immunosuppressionTherefore, it is of great significance to study the molecular mechanism of local and systemic immunosuppressive glioma, which can provide a basis for the diagnosis and treatment of gliomaJaved NAgrewala of the Institute of Immunology at the Indian Institute of Technology and the CSIR Institute of Microbiology Technology, among others, has conducted studies to clarify the correlation between tumor-related macrophage phenotypes phenotypes and glioma progression, and the results are published in cancerotherl immun in December 2019the results of the study
the authors studied the gene expression spectrum and immune cell immersion of different levels of glioma through a gene chip and compared it with normal tissue on the side of the tumorThe results showed an increase in TAM leaching in the microenvironment of glioma, most of which were inactivated macrophages (M2c subtypes) and confirmed by the increase in expression of M2c subtype-specific genes (CD163, IL10RA and CCL18)In contrast, the CCL3 and CCL5 genes associated with antitumor macrophages (M1 subtype macrophages) were less expressed in gliomasTo verify the observations of chip data, the researchers used the Cancer Genome Map (TCGA) to detect expression levels such as CCL3, CD163, IL-10 and TFG-beta in patients with low-grade gliomas in public databases; As a result, M2 subtype macrophages increased in high-level gliomas, while fewer M1 subtype macrophages were presentWith the increase of the malignant degree of glioma, the number of anti-tumor macrophages, or M1 subtype macrophages, decreasedthe researchers calculated the CD163/CCL3 ratio representing the balance between M2c subtype and M1 subtype TAM, and found that higher expression of CD163/CCL3 gene ratio was associated with the progression of gliomaKaplan-Meier survival curve showed that patients with lower expression of M2c subtype markers (CD163) and higher expression of M1 subtype markers (CCL3) had better survival rates in glioma patients , glioma-induced inhibition is not limited to the tumor microenvironment, but also manifested in peripheral blood By collecting whole blood to detect systemic immune responsein in peripheral blood, the researchers found that M2 subtype macrophages, bone marrow-derived inhibitory cells and PD-1-CD4 T cells were dominant in glioma patients, indicating that glioma patients were not only inhibited in the brain's local immunity, but also by whole body immunity conclusions the final authors note that the main findings of the study are: (1) glioma grading may be related to the CD163/CCL3 ratio; (2) Most of the TAM phenotypes in human glioma are M2c subtypes, and the cell type may be one of the targets for future treatment (3) Lower expression of M2c subtype markers (CD163) and higher expression of M1 subtype markers (CCL3) in patients with low-level gliomaweres were associated with better survival rates in patients (4) The level increase of M2 subtype macrophages, bone marrow-derived inhibitory cells and PD-1-CD4 T cells in peripheral blood in glioma patients can be used for early diagnosis of glioma.