Supplementation with a high-glucose drink stimulates anti-tumor immune responses to glioblastoma via gut microbiota modulation

• Published in: Cell reports (Cambridge) 2023-10, Vol.42 (10), p.113220-113220, Article 113220
• Main Authors: Kim, Jaeho, Kim, Yumin, La, Jeongwoo, Park, Won Hyung, Kim, Hyun-Jin, Park, Sang Hee, Ku, Keun Bon, Kang, Byeong Hoon, Lim, Juhee, Kwon, Myoung Seung, Lee, Heung Kyu
• Format: Article
• Language: English
• Subjects: anti-tumor immune response; glioblastoma; gut microbiota; high-glucose drink; immune checkpoint inhibitors
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.113220

A high-sugar diet induces lifestyle-associated metabolic diseases, such as obesity and diabetes, which may underlie the pro-tumor effects of a high-sugar diet. We supply GL261 syngeneic glioblastoma (GBM) mice with a short-term high-glucose drink (HGD) and find an increased survival rate with no evidence of metabolic disease. Modulation of the gut microbiota through HGD supplementation is critical for enhancing the anti-tumor immune response. Single-cell RNA sequencing shows that gut microbiota modulation by HGD supplementation increases the T cell-mediated anti-tumor immune response in GBM mice. We find that the cytotoxic CD4+ T cell population in GBM is increased due to synergy with anti-programmed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors, but this effect depends upon HGD supplementation. Thus, we determine that HGD supplementation enhances anti-tumor immune responses in GBM mice through gut microbiota modulation and suggest that the role of HGD supplementation in GBM should be re-examined. [Display omitted] •A high-glucose drink (HGD) increases survival rates in a glioblastoma mouse model•HGD increased anti-tumor immunity in glioblastoma via modulation of the gut microbiota•HGD induces gut colonization of the Desulfovibrionaceae family in GBM mice•Desulfovibrio vulgaris plays a significant role in synergy with anti-PD-1 Kim et al. report that a high-glucose drink increases survival outcomes in a glioblastoma mouse model. A high-glucose drink induces gut colonization of Desulfovibrionaceae, leading to enhanced anti-tumor immunity in the tumor microenvironment. Desulfovibrio vulgaris was found to have a synergistic effect with anti-PD-1 immune checkpoint blockade.