The antitumor efficacy of cancer immunotherapy can correlate with the presence of certain bacterial species within the gut microbiome. However, many of the molecular mechanisms that influence host response to immunotherapy remain elusive. In this study, we show that members of the bacterial genus Enterococcus improve checkpoint inhibitor immunotherapy in mouse tumor models. Active enterococci express and secrete orthologs of the NlpC/p60 peptidoglycan hydrolase SagA that generate immune-active muropeptides. Expression of SagA in nonprotective E. faecalis was sufficient to promote immunotherapy response, and its activity required the peptidoglycan sensor NOD2. Notably, SagA-engineered probiotics or synthetic muropeptides also augmented anti–PD-L1 antitumor efficacy. Taken together, our data suggest that microbiota species with specialized peptidoglycan remodeling activity and muropeptide-based therapeutics may enhance cancer immunotherapy and could be leveraged as next-generation adjuvants.
The ability to tailor
plasma membranes with specific glycans may
enable the control of signaling events that are critical for proper
development and function. We report a method to modify cell surfaces
with specific sulfated chondroitin sulfate (CS) glycosaminoglycans
using chemically modified liposomes. Neurons engineered to display
CS-E-enriched polysaccharides exhibited increased activation of neurotrophin-mediated
signaling pathways and enhanced axonal growth. This approach provides
a facile, general route to tailor cell membranes with biologically
active glycans and demonstrates the potential to direct important
cellular events through cell-surface glycan engineering.
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