Radiotherapy-binding anti-PD-L1 antibody activates macrophages to induce remote effects of GBM treatment

Most glioblastomas (GBMs) recur in the 2cm range of the original tumor after surgery and standard chemotherapyTherefore, a significant improvement in the survival of GBM patients may require the use of the immune system to kill drug-resistant tumor cells or residual tumors near the primary tumorPrevious studies have shown that radiotherapy combined with anti-PD-L1 antibody immunotherapy showed some efficacy in clinical Phase II trials of non-methylated glioblastomaHowever, the effect of its mechanism and remote effect on survival rate is still unclearEric CHolland of the Human Biology Transformed Cancer Research Unit at the Fred Hutchinson Cancer Research Center in Seattle, Wash., USA, and others used the RCAS/Tva mouse GBM model to study the transsensitive effects of radiotherapy in combination with anti-PD-L1 antibody therapy, published online December 2019 in Neuro-Oncologythe studythe researchers used the RCAS/Tva mouse GBM model to establish a radiation-underlying GBM in the hemisphere of the brain that was exposed to luciferase expression on one side, and GBM on the other side, which showed the expression of luciferin asease or EGFRvIII, which was not exposed to radiationThe former is an improved, immunized, genetically driven glioma model in mice (forced PDGF expression and PTEN deletion), and the latter is an unradiated tumor that expresses fluoxexein assymitase (PDGF-fluoroprosone) to reflect the post-remote effect of anti-PD-L1 antibody immunotherapythe results of the studythe establishment of animal models of tumors in mice, the researchers used biofluorescence or MRI imaging to observe tumor growth, and found that tumor cultivation was successful and began treatmentDuring radiotherapy, the shielding side of the brain hemisphere and other non-target tissues of the body to avoid radiation, on the premise of radiation, the radiotherapy side of the hemisphere at a dose of 10 Gy radiationLow-dose endotoxins, IgG2b, anti-PD-L1, and anti-PD1 immunotherapy are given from the day of radiotherapy, once a day until the endResults showed that the RCAS/TV-a mouse GBM model received radiotherapy and systemic anti-PD-L1 antibody combination therapy, which was better than systemic anti-PD-L1 antibody monotherapyOne side GBM radiotherapy, play a role in enhancing anti-PD-L1 antibody immunotherapy on the unradioraped side GBM effect, that is, the far-off effect Anti-PD-L1 antibodies alone do not induce temporary tumor retreat (TTR) or persistent tumor retreat (STR) in any mouse Further studies have found that local radiotherapy and systemic anti-PD-L1 antibody immunotherapy promote macrophages and T-cell immersion in tumors, suggesting that the far-off effect is to initiate ERK-mediated, bone marrow-derived macrophages by anti-PD-L1 antibody therapy, which has the significance of moderately improving the survival of mice The far-flotated effect of radiotherapy in combination with anti-PD-L1 antibody immunotherapy is associated with macrophages and T-cell immersion, which significantly prolongs survival conclusions
the final authors point out that the experimental study of the RCAS/Tv-a mouse system model found that in glioblastoma, anti-PD-L1 antibody immunotherapy enhances the far-flung effect of radiation therapy by activating T cells and macrophages, prolonging the survival of experimental animals.