CD73 is a specific target for improving GBM immunotherapy

Immunotherapy is a treatment that kills tumor cells by enhancing the vitality of the body's autoimmune cells and activating immune capacityAt the end of the 20th century, scientists used cytokines such as leukone and interferon to activate immune cells extracted from the patient's body in vitro and then return them back to the patient to enhance their anti-tumor effectAt the beginning of the 21st century, dendicotic cells (DC) were found to transmit information to enhance t lymphocytes' anti-tumor ability, or to use genetic technology to transmit receptors that identify tumor cells directly on T cells to chimeric antigen receptor T-cell immunotherapy (Chimeric Receptor T-Cell Immunotherapy, CAR-T)Under normal circumstances, once the risk of infection or tumor is controlled, immune cells produce self-suppressing molecules called "immune checkpoints", but many tumor cells mutate and use this molecule to "trick" immune cells to escapeIn this regard, the development of immuno-checkpoint inhibitors, such as CTLA-4 monoantigen and PD-1/PD-L1 monoantigen, to extend the activation period of the immune response, play a therapeutic role, named "immune checkpoint therapy" (ICT), and has been shown to have some effect on melanoma, non-small cell lung cancer and lymphomaBut glioblastoma (GBM) does not respond well to immunotherapySangeeta Goswami of Urology Oncology at the University of Texas Anderson Cancer Center and others found that CD73 could be a specific target for GBM immunotherapy, the results of which were published online in Nature Medicine in December 2019research methods
through immunohistification analysis, found that the GBM specimen sorghum content of CD68 plus myelin cell is high, high expression CD68 plus macrophages, also expressed CD73CD73 is an external nucleotide enzyme that has been shown to promote tumor development and induce immunosuppression in GBMIt was also found that macrophages expressing CD73 may be involved in GBM tumor microenvironmentsFurther use of cancer genome mapping (TCGA) studies showed that the high expression of cd73 gene was significantly negatively correlated with the total survival rate of GBM patientsresearchers extracted peripheral blood mononucleosis in PATIENTs with conventional and immunotherapy, evaluated the results of using mass spectrometry cell analysis techniques and single-cell RNA sequencing techniques, and found that there was a unique CD73 myelin cell cluster in GBM after anti-PD-1 treatmentThe authors compared the differences between GBM samples after anti-PD-1 treatment and GBM samples without anti-PD-1 treatmentIn 7 gbM patients who were not treated with PD-1 and 5 were treated with pembrolizumab, there were 17 cluster phenotypes, 3 of which were CD73 myelin cell clustersThe three CD73 myelin cell clusters remained and did not change after ICT treatment, indicating that PD-1 therapy did not significantly alter the microenvironment of GBM tumorsThe authors believe that the presence of CD73 myelin cells causes T-cells to be under-submerged, so PD-1 is not effective in treating GBM the results the authors used GBM cell line GL261 to make GBM animal models from wild-type C57BL/6 mice and mice that knocked out the CD73 gene The difference smaller in immune cell immersion was assessed by comparative immunoanalysis methods to assess the differences between wild type and the two groups of animal models that knocked out the CD73 gene The results showed that the absence of CD73 in the GBM model of mice improved the survival rate of tumor-carrying mice by regulating the subgroup of myelin cells in tumors Then, in the specific time after the tumor of the mice, the celiac injection CTLA-4 monoantigen and PD-1/PD-L1 monoantigen, respectively, showed that in mice that knocked out the CD73 gene, the immune stimulation-induced macrophage phenotype change affected the efficacy of ICT, cd73 deficiency can improve CTLA-4 monoantigen and PD-1 monoantigen in mice conclusion
the final authors believe that anti-CD73 antibodies have achieved better efficacy in early clinical and clinical studies for the treatment of GBM Therefore, CD73 is a specific target to improve the immunotherapy of glioblastoma, and proposed to CD73 as the target, combined With PD-1 and CTLA-4 double blocking treatment strategy.