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To overcome immune suppression in the clinic, antigen-expressing viruses and bacteria have been developed to induce antitumor immunity. However, the safety and targeting specificity are the main concerns of using bacteria in clinical practice as antitumor agents. In our previous studies, we have developed an attenuated bacterial strain (<jats:italic>Brucella melitensis<\/jats:italic> 16M \u2206<jats:italic>vjbR<\/jats:italic>, henceforth Bm\u2206<jats:italic>vjbR<\/jats:italic>) for clinical use, which is safe in all tested animal models and has been removed from the select agent list by the Centers for Disease Control and Prevention. In this study, we demonstrated that Bm\u2206<jats:italic>vjbR<\/jats:italic> homed to tumor tissue and improved the TME in a murine model of solid cancer. In addition, live Bm\u2206<jats:italic>vjbR<\/jats:italic> promoted proinflammatory M1 polarization of tumor macrophages and increased the number and activity of CD8<jats:sup>+<\/jats:sup> T cells in the tumor. In a murine colon adenocarcinoma model, when combined with adoptive transfer of tumor-specific carcinoembryonic antigen chimeric antigen receptor CD8<jats:sup>+<\/jats:sup> T cells, tumor cell growth and proliferation was almost completely abrogated, and host survival was 100%. Taken together, these findings demonstrate that the live attenuated bacterial treatment can defeat cancer resistance to chimeric antigen receptor T-cell therapy by remodeling the TME to promote macrophage and T cell-mediated antitumor immunity.<\/jats:p>","DOI":"10.1136\/jitc-2021-003760","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T11:45:16Z","timestamp":1641383116000},"page":"e003760","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Live attenuated bacterium limits cancer resistance to CAR-T therapy by remodeling the tumor microenvironment"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3742-7214","authenticated-orcid":false,"given":"Fengguang","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jugal K","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi S","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77802, USA"},{"name":"Department of Immunology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Ming","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"A Ficht","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C","family":"Alaniz","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9734-6176","authenticated-orcid":false,"given":"Jianxun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul De","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77802, USA"},{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,1,5]]},"reference":[{"key":"2025100300551165000_10.1.e003760.1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3394"},{"key":"2025100300551165000_10.1.e003760.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3245"},{"key":"2025100300551165000_10.1.e003760.3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41416-018-0327-z","article-title":"The clinical role of the Tme in solid cancer","volume":"120","author":"Giraldo","year":"2019","journal-title":"Br J Cancer"},{"key":"2025100300551165000_10.1.e003760.4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28045"},{"key":"2025100300551165000_10.1.e003760.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211287110"},{"key":"2025100300551165000_10.1.e003760.6","unstructured":"Selvanesan BC , Chandra D , Quispe-Tintaya W . 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