Tumor-related reactive astrocytes can form an immunosuppressive environment in GBM

Dieter Henrik Heiland of the Translational Neurotumor Research Group at the University Of Freiburg Medical Center in Germany has found that the interaction of glioma-associated star-shaped glial cells and small glial cells can form an immune escape microenvironment for gliomasThe results were published in nature Communications in June 2019- Excerpted from article chapter
Ref: Henrik Heiland D,et al.
 Nat Commun2019 Jun 11;10 (1):2541doi: 10.1038/s41467-019-10493-6Reprogrammed at the transcription group level of reactive astrocytes afterbrain damage, inflammation, and degenerative diseasesIn malignant brain tumors, the function of tumor-related reactive astrocytes and their synergies with other cells in the microenvironment is poorly understoodDieter Henrik Heiland of the Translational Neurotumor Research Group at the University Of Freiburg Medical Center in Germany has found that the interaction of glioma-associated star-shaped glial cells and small glial cells can form an immune escape microenvironment for gliomasThe results were published in nature Communications in June 2019the authors first sequenced RNA for reactive astrocytes in different human brain tissue specimensGenomic enrichment analysis showed significant improvement in the IFN-xenon and JAK/STAT signaling pathways in tumor-related astrocytessubsequently, the authors verified that tumor-related astrocytes were widely present in gliomas and that the glioma specimens were immunizedThe staining results showed that CD274-/GFAP-plus cells were concentrated in large numbers at the glioic reaction scar during the tumor, while macrophages and small glial cells from the myelin source were not concentrated here (Figure 1) Figure 1 Expression of CD274-star glial cells in gliomas because astrocytes themselves do not accept the stimulation of inflammatory reaction factors, their reactions need to be signaled by small glial cells after they occur The authors used an experimental model to remove small glial cells to sequence RNA for astrocytes under different conditions In the presence of small glial cells, it was found that the JAK/STAT pathway in astrocytes was significantly activated (Figure 2) Figure 2 The transcription algeout spectrum of astrocytes was detected in an experimental model for the removal of small glial cells then, the authors sequenced transcription clusters of small glial cells and found that most of the activation of small glial cells was not affected by co-culture of astrocytes However, in the presence of astrocytes, the metabolic abnormality of the microenvironment improved and the concentration of IL-10 increased results showed that immunosuppression in tumor microenvironment was formed by the synergy between small glial cells and astrocytes, as well as JAK/STAT pathway activation and IL-10 elevation After using THE JAK inhibitor Ruxolitinib, the authors found that the tumor decreased significantly, the number of astrocytes activated decreased, and the pro-inflammatory factor increased and the inhibitory inflammatory factor decreased significantly , inhibiting the JAK/STAT pathway can transform the microenvironment of pro-inflammatory cytokines and anti-inflammatory cytokines into an inflammatory environment The interaction of astrocytes and small glial cells promotes the formation of immunosuppressive microenvironments, indicating that tumor-related astrocytes are significantly associated with inflammatory responses.