Beneficial Effect of Antibiotics and Microbial Metabolites on Expanded Vδ2Vγ9 T Cells in Hepatocellular Carcinoma Immunotherapy
Jiajia Han, Siya Zhang, Yi Xu, Yongsheng Pang, Xue Zhang, Yu Hu, Hui Chen, Wanjun Chen, Jianmin Zhang, Wei He
Abstract
Animal experiments and clinical trials have shown that the gut microbiota modulate host immunity and the immune checkpoint-mediated responses to tumor cells. However, it remains unclear whether microbiota can also play a role in tumor immune response of gamma delta T cell, a kind of cells target cancer directly. Here, we are reporting the microbiota dysbiosis induced by antibiotics enhanced gamma delta T cell efficacy during tumor therapy in a mouse model. Further microbiota and metabolite analysis revealed that the alteration of gamma delta T cell cytotoxicity might be closely associated with specific metabolites, which are produced by intestinal bacteria and stimulate gamma delta T cell to release more cytotoxic cytokines, such as granzyme B and perforin. Among the metabolites that we analyzed, 3-Indolepropionic acid (IPA) showed the highest concentration in antibiotic-treated mice and can improve the cytotoxic ability of gamma delta T cells both in vitro and in vivo. Our research determined how the gut microbiota can influence the antitumor ability of gamma delta T cells and identified potential intermediate molecules that connect the gut microbiota and gamma delta T cells.