The role of diet-induced gut microbiota modulation in the regulation of anti-tumor immune responses against glioblastoma

Abstract

Although remarkable advances have been made in the treatment of malignant tumors over the past few decades, the treatment of glioblastoma has not shown great progress. Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein-1 (anti-PD-1), have shown excellent effects against various tumors, including melanoma, but have failed to improve on the effects of existing treatments in several clinical trials in glioblastoma. Furthermore, the gut microbiota was revealed to be closely related to the anti-tumor immune response and enhance the effect of ICIs. This study found that the survival rate of glioblastoma was increased through a high-glucose diet (HGD) and showed that the change in the gut microbiota induced by the HGD caused this difference in the survival rate of glioblastoma. In addition, phenotypic analysis of immune cells in the glioblastoma tumor microenvironment showed that the HGD increased the immune response of cytotoxic CD8+ T cells. Moreover, an experiment performed to compare survival rates confirmed that this increase in the anti-tumor immune response mediated by the HGD increased the effect of the ICI. Furthermore, we identified specific gut microbiota species that are increased by the HGD and found that these species play an important role in enhancing the anti-tumor immune response. Consequently, this study reveals that an HGD induces changes in the gut microbiota, and these changes could increase the survival rate of glioblastoma by upregulation of anti-tumor immunity.