In August 14th, Cancer Cell published an article titled with Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade from the molecular department of Neurosurgery Laboratory and Brain Tumor Research Center. Now let us discuss the treatment effect of interleukin 12 expressed by replication oncolytic herpes simplex virus (oHSV) in glioma in oncolytic virus engineering.
005 GSCs has stem cell attributes. So researchers analyzed the important indicators of PD-L1, finding that in vitro PD-L1 will be induced by IFN- gamma for proliferation, and in vivo will not be affected by G47 Delta -mIL12. However, the induction experiments in vivo lead to the proliferation of tumor infiltrating CD3+ lymphocytes, suggesting that virus mediated changes promoted inflammatory response.
Next, the researchers explored the inhibitory effects of G47 Delta -mIL12 and anti PD-L1 antibody on the immune checkpoint, and found that the combined effect did not significantly improve than the single effect. Through the analysis of the flow cytometry data, the researchers found that G47 Delta -mIL12 alone and used with anti CTLA-4 antibody will both promote the growth of T cells, but this was not enough to cure mice.
However, the combination of G47 Delta -mIL12, anti CTLA-4 antibody and anti PD-L1 antibody showed that the cure rate of GSCs mice was high, and almost no recurrence was found in mice. In CT-2A glioma model. Three combination also played a significant effect.
Next, the researchers used multicolor flow cytometry and immunohistochemical for complementary analysis of mouse brain. Compared with double checkpoint inhibitors or G47D-mIL12, three combination therapy caused major changes are increase of Treg / Teff and decrease of tumor cells. Through the analysis of immunohistochemical markers, the researchers found that CD68+, pSTAT1+, iNOS+ and Ki-67+ cells were significantly increased in the triple group, indicating that triple therapy induced the activation of T cells and the influx of TAMs & M1.
In order to elucidate the relationship between the changes observed in tumor infiltrating immune cells and the triple therapy, researchers studied the depletion of antibodies in CD4+ and CD8+ cells by using peripheral macrophages to inhibit CSF-1R targeting TAM, finding that the liposomal chloride blocked the triple therapy, and the anti CD4 antibody completely eliminated all the effects to reduce the TAM.
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