Microbial hydrogen “manufactory” for enhanced gas therapy and self-activated immunotherapy via reduced immune escape

Abstract

Background: As an antioxidant, hydrogen (H2) can selectively react with the highly toxic hydroxyl radical (·OH) in tumor cells to break the balance of reactive oxygen species (ROS) and cause oxidative stress. However, due to the high diffusibility and storage difficulty of hydrogen, it is impossible to achieve long-term release at the tumor site, which highly limited their therapeutic effect. Results: Photosynthetic bacteria (PSB) release a large amount of hydrogen to break the balance of oxidative stress. In addition, as a nontoxic bacterium, PSB could stimulate the immune response and increase the infiltration of CD4+ and CD8+ T cells. More interestingly, we found that hydrogen therapy induced by our live PSB did not lead to the up-regulation of PD-L1 after stimulating the immune response, which could avoid the tumor immune escape. Conclusion: Hydrogen-immunotherapy significantly kills tumor cells. We believe that our live microbial hydrogen production system provides a new strategy for cancer hydrogen treatment combining with enhanced immunotherapy without up-regulating PD-L1. Graphical Abstract: [Figure not available: see fulltext.].