The response of super mutant gliomas to immuno-checkpoint inhibitors is heterogeneic

Blocking immune checkpoints such as PD-1 and CTLA-4 can reduce inhibition of T cells, restore T-cell activation and proliferation, and reactivate anti-tumor immunity.
point-of-immune checkpoint inhibitors (ICB) targeted at PD-1 and CTLA-4 have been increasingly used in solid tumor therapy and have produced long-lasting responses in a significant number of patients to improve survival rates.
, however, malignant brain tumors, such as glioblastoma (GBM), are resistant to ICC, and only a few ultra-mutant GBMs respond.
Katrin Aslan of Neuroimmune and Brain Tumor Immunology at the Heidelberg Cancer Research Center in Germany, etc., established animal models to study the drug resistance mechanism of super mutant gliomas to PD-1 monoantimmune and CTLA-4 monoantigens, and found that immune escape involves a variety of factors and is heterogeneous;
the study, the researchers inoculated GL261 in C57Bl/6J mice in groups d13, d19, and d26, and injected 250 μg of PD-1 monoantigen and 100?g of CTLA-4 monoantigen (ICB plus) or control agent, respectively.
then used MRI imaging to monitor the growth of gliomas, comparing the response patterns of ICC and control agents in mice treated with holoma.
mice were divided into the ICB Reaction (ICB R) group and the ICB Non-Response (ICB NR) group.
d26 to take IB R and IB NR group mouse tumors for exon sequencing.
used imaging histology to evaluate ICC reaction and false progress.
mice MRI was prompted to have false progression in mice in the ICB R group, and 77.23% of mice in the ICB R group increased in volume at the beginning of treatment and then rapidly shrunk, with only 19.8% of mice in the ICB R group having a reduced lesion volume shortly after treatment, with no false progression.
ICB NR mice, the immune function of anti-tumor T cells was significantly impaired.
ICB NR group had significantly less immersion of T-cells (TIL) in mouse tumors than in the ICB R group.
ICCB R tumors, there were significantly fewer regulatory Treg cells in CD4-CD25-FOXP3-Treg, and Treg played an immune-suppressing role, which could explain some of the reasons for the ICCR R group's response to tumors. Analysis of
multi-parameter flow cytometers found that in mice in the IB R group, inhibitory cell immersion in the myelin system, such as monocytes, single-nucleal source lymphocytes (MDCs) and macrophages, were significantly reduced compared to mice in the IB NR group.
results suggest that inhibiting lymphocytes is the main cause of ICC failure.
ICCB NR group mice associated with tumors from myelin coculture inhibition cells and T cells were more obvious than IB R group, which inhibited cd4-T cell proliferation, but did not inhibit CD8-T cells.
in tumor-immersed lymphocytes in IB R tumors, the ratio of CD80 cells was significantly lower than that of IB NR and control groups, indicating that the PD-L1/PD-1/CD80 axis inhibited CD4-positive tumor-immersed lymphocytes.
ICC therapy, which is jointly targeted at PD-1 and CTLA-4, inhibits the growth of glioma in mice.
the results show that the immune escape of tumor cells is involved by many factors and immunosuppressants, which play a key role in drug resistance to PD-1 and CTLA-4 inhibitors.
the causes of anti-tumor T-cell proliferation and inhibition have strong heterogeneity in glioma, which provides important ideas for future immunotherapy.
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