A clinic responder-derived defined microbial consortium enhances anti-PD-1 immunotherapy efficacy in mice

ABSTRACT: Growing evidence supports the gut microbiota as a promising target for enhancing the efficacy of cancer immunotherapy. However, the success of microbiota-targeting interventions has been limited, partly due to interindividual microbial heterogeneity. Here, we designed and constructed a defined consortium (RCom) of 15 bacterial species that are associated with improved clinic response to anti-PD-1 treatment and were mostly isolated from the feces of responder patients. Through in silico prediction and experimental characterization in vitro and in vivo, we demonstrated that the RCom is a relatively cooperative community, in which five Bacteroidetes species and ten Firmicutes species act together to establish optimal engraftment and produce immunomodulatory metabolites. Despite a profound heterogeneity of the baseline gut microbiota, oral supplementation of the RCom consistently improved the anti-tumor activity of anti-PD-1 by increasing intratumoral infiltration and cytotoxic activity of CD8+ T cells in syngeneic tumor models. Moreover, administration of the RCom circumvented the anti-PD-1 resistance in mice conferred by fecal microbiota transplantation from individual non-responsive patients. The RCom is thus a potential adjuvant to augment responsiveness to anti-PD-1 therapy in cancer

INSTRUMENT(S):

ORGANISM(S): Firmicutes Bacterium Hgw-firmicutes-5

SUBMITTER: Haiyan Zhou  

LAB HEAD: Chen Yang

PROVIDER: PXD064618 | Pride | 2026-01-14

REPOSITORIES: Pride