biostudies-literatureGuo YNational Key Research and Development Projecte12744https://www.ebi.ac.uk/biostudies/studies/S-EPMC12697889biostudies-literatureUnknown12(46)Recent progress in synthetic biology has empowered engineered probiotics to sense tumor-specific physicochemical signals, thereby facilitating targeted in situ drug delivery. Here, an engineered probiotic consortium capable of integrating multiple tumor microenvironment (TME) signals and orchestrating multi-therapeutic payloads release through an orthogonal quorum-sensing system is designed. The probiotic consortium can respond to three characteristic TME parameters, pH, hypoxia, and high-lactate levels, in order to achieve controlled release of lactate depletion enzyme (LdhA) for metabolic environment improvement and the programmed death ligand 1 (PD-L1) nanobody for immune checkpoint inhibition. Using the humanized PD-1 mouse model bearing hPD-L1 MC38 tumor and the humanized peripheral bAdvanced science (Weinheim, Baden-Wurttemberg, Germany)An Engineered Probiotic Consortium Based on Quorum-Sensing for Colorectal Cancer Immunotherapy.PMC126978892024YFA0918500Wu JKang GGao MZhu ZGuo YZhang YHuang HGao XYuan HWang ZWang LYin JfalseAn Engineered Probiotic Consortium Based on Quorum-Sensing for Colorectal Cancer Immunotherapy.Recent progress in synthetic biology has empowered engineered probiotics to sense tumor-specific physicochemical signals, thereby facilitating targeted in situ drug delivery. Here, an engineered probiotic consortium capable of integrating multiple tumor microenvironment (TME) signals and orchestrating multi-therapeutic payloads release through an orthogonal quorum-sensing system is designed. The probiotic consortium can respond to three characteristic TME parameters, pH, hypoxia, and high-lactate levels, in order to achieve controlled release of lactate depletion enzyme (LdhA) for metabolic environment improvement and the programmed death ligand 1 (PD-L1) nanobody for immune checkpoint inhibition. Using the humanized PD-1 mouse model bearing hPD-L1 MC38 tumor and the humanized peripheral b2025-01-01T00:00:00Z2025 Dec2026-06-06T01:19:00.949Z2026-05-24T03:12:31.222ZS-EPMC126978894099988510.1002/advs.202512744