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Although modulating intratumoral lactate is a promising strategy, tumor\u2010targeted interventions remain limited. Here, we developed an engineered probiotic, Lac\u2010EcN, capable of targeted lactate consumption within the TME. Lac\u2010EcN reduces intratumoral lactate levels by over 60% and alleviates tumor acidosis, accompanied by reversal of aberrant NFAT1 nuclear translocation in Tregs and restoration of effector molecule production by cytotoxic T cells. In B16\u2010F10 melanoma and MC\u201038 colorectal carcinoma models, Lac\u2010EcN combined with anti\u2010PD\u20101 improves tumor inhibition and extends survival. These results position engineered probiotics as a platform for targeted metabolic intervention in the TME, integrating metabolic reprogramming with immune checkpoint blockade.<\/jats:p>","DOI":"10.1002\/adhm.71316","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:36:36Z","timestamp":1780378596000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lactate\u2010Depleting Engineered Probiotics Remodel the Tumor Microenvironment and Enhance PD\u20101 Blockade"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7011-9169","authenticated-orcid":false,"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Biomedical Engineering College of Life Sciences Qingdao University  Qingdao 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