Boosting Immune Checkpoint Therapy Efficacy of Pancreatic Cancer by Cell‐Anchoring Probiotic

Abstract Live bacteria in tumor sites can recruit and activate T cells, enhancing the efficacy of immune checkpoint therapy (ICT) for cancer. However, the low bacterial presence within tumors may insufficiently trigger ICT. Here bio‐orthogonal click chemistry is utilized to develop cell‐anchoring probiotic that significantly improves bacterial colonization and boosts efficacy of ICT in pancreatic ductal adenocarcinoma (PDAC). The strategy involves metabolically labeling pancreatic cancer cells with azide groups both in vitro and in vivo, facilitating the covalent anchoring of dibenzocyclooctyne‐modified probiotic. This stuyd observes a remarkable increase in colonization by Bifidobacterium within orthotopic pancreatic tumors in vivo and enhanced effector CD8 + T cell infiltration, which is beneficial for cancer immunotherapy. When combined with immune checkpoint inhibitor ( α PD‐L1), the approach shows potent suppression of tumor growth in both orthotopic pancreatic cancer and transgenic animal models. This work may provide an unprecedented strategy to increase bacterial colonization and regulate T‐cell responses in vivo, offering a new avenue for cancer immunotherapy.