{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:20:27Z","timestamp":1793373627853,"version":"4.5.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"52","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31900988"],"award-info":[{"award-number":["31900988"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:p>\n                    Inhibiting indoleamine 2,3 dioxygenase (IDO) for anticancer therapy has garnered significant attention in recent years. However, current IDO inhibitors face significant challenges which limit their clinical application. Here, we genetically engineered a high tryptophan-expressing\n                    <jats:italic toggle=\"yes\">Clostridium butyricum<\/jats:italic>\n                    (L-Trp CB) strain that can colonize tumors strictly following systemic administration. We revealed that butyrate produced by L-Trp CB can inhibit IDO activity, preventing tryptophan catabolism and kynurenine accumulation in tumors. In addition, the large released tryptophan by L-Trp CB can provide discrete signals that support CD8+ T cell activation and energy metabolism within the tumor microenvironment. We observed that L-Trp CB significantly restored the proportion and function of CD8+ T cells, leading to significantly delayed tumor growth in both mouse and rabbit multiple tumor models with limited side effects. We here provide a synthetic biology treatment strategy for enhanced tumor immunotherapy by inhibiting IDO activity and reprogramming CD8+ T cell response in tumors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2412070121","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T13:38:39Z","timestamp":1734529119000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":40,"title":["Engineering bacteria for cancer immunotherapy by inhibiting IDO activity and reprogramming CD8+ T cell response"],"prefix":"10.1073","volume":"121","author":[{"given":"Heng","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano and Soft Materials, Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano and Soft Materials, Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenlu","family":"Yao","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano and Soft Materials, Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaxing","family":"Dai","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano and Soft Materials, Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano and Soft Materials, Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano and Soft Materials, Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Affiliated Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Shi","sequence":"additional","affiliation":[{"name":"Medical College of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8054-3472","authenticated-orcid":false,"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterial and Immunoengineering, Institute of Functional Nano and Soft Materials, Soochow University","place":["Suzhou, Jiangsu, 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Wang Engineering bacteria for Cancer Immunotherapy by Inhibiting IDO activity and Reprogramming CD8+ T cells Response. NCBI BioProject. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/1193661. 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