{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:45:33Z","timestamp":1782891933104,"version":"3.54.5"},"reference-count":59,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"am","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["HT94252310067"],"award-info":[{"award-number":["HT94252310067"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH1910602"],"award-info":[{"award-number":["W81XWH1910602"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008637","name":"Center for Strategic Scientific Initiatives, National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA188382"],"award-info":[{"award-number":["R01CA188382"]}],"id":[{"id":"10.13039\/100008637","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["enviromicro-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbial Biotechnology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Immunotherapies have revolutionized cancer treatment. These treatments rely on immune cell activation in tumours, which limits the number of patients that respond. Inflammatory molecules, like lipopolysaccharides (LPS), can activate innate immune cells, which convert tumour microenvironments from cold to hot, and increase therapeutic efficacy. However, systemic delivery of lipopolysaccharides (LPS) can induce cytokine storm. In this work, we developed immune\u2010controlling Salmonella (ICS) that only produce LPS in tumours after colonization and systemic clearance. We tuned the expression of\n                    <jats:italic>msbB<\/jats:italic>\n                    , which controls production of immunogenic LPS, by optimizing its ribosomal binding sites and protein degradation tags. This genetic system induced a controllable inflammatory response and increased dendritic cell cross\u2010presentation in\u00a0vitro. The strong off state did not induce TNF\u03b1 production and prevented adverse events when injected into mice. The accumulation of ICS in tumours after intravenous injection focused immune responses specifically to tumours. Tumour\u2010specific expression of\n                    <jats:italic>msbB<\/jats:italic>\n                    increased infiltration of immune cells, activated monocytes and neutrophils, increased tumour levels of IL\u20106, and activated CD8 T cells in draining lymph nodes. These immune responses reduced tumour growth and increased mouse survival. By increasing the efficacy of bacterial anti\u2010cancer therapy, localized production of LPS could provide increased options to patients with immune\u2010resistant cancers.\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.14461","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T10:33:58Z","timestamp":1715942038000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Controlled production of lipopolysaccharides increases immune activation in Salmonella treatments of cancer"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-8945","authenticated-orcid":false,"given":"Lars M.","family":"Howell","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering University of Massachusetts Amherst  Amherst Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9302-9712","authenticated-orcid":false,"given":"Simin","family":"Manole","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology Program University of Massachusetts Amherst  Amherst Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6567-5893","authenticated-orcid":false,"given":"Alec R.","family":"Reitter","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering University of Massachusetts Amherst  Amherst Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4745-753X","authenticated-orcid":false,"given":"Neil S.","family":"Forbes","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering University of Massachusetts Amherst  Amherst Massachusetts USA"},{"name":"Molecular and Cellular Biology Program University of Massachusetts Amherst  Amherst Massachusetts USA"},{"name":"Institute for Applied Life Sciences, University of Massachusetts Amherst  Amherst Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1586\/erv.12.35"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-0552"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.7.1287"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26407-4"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026043388213"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(97)01115-8"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/315497"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302569"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.8.4102"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/12.6.807"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-004-0610-0"},{"key":"e_1_2_8_13_1","first-page":"843","article-title":"Attenuated salmonella enterica typhimurium reduces tumor burden in an autochthonous breast cancer model","volume":"35","author":"Drees J.","year":"2015","journal-title":"Anticancer Research"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.10.5268"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1996.d01-785.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0381-3"},{"key":"e_1_2_8_17_1","first-page":"5188","article-title":"Sparse initial entrapment of systemically injected salmonella typhimurium leads to heterogeneous accumulation within tumors","volume":"63","author":"Forbes N.S.","year":"2003","journal-title":"Cancer Research"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1972.tb02524.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/cgt.2011.10"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-021-00635-3"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.8.1343"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(00)00149-2"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3182939831"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.2.926"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.007"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048913"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-014-1543-x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229647"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/75843"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2618"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2022.12.012"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.5.2589"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-1808"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05524-11"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00123-12"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104351"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006692"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3727\/096504001108747512"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2013.00003"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40635-018-0184-3"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.04.027"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2017.03.009"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006600"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200703-515OC"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00230"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2016.10.005"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1568"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0436-x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02529735"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-7-233"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.06.001"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071990"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2010.02.004"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2021.153723"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01590-13"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2019.09.018"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.20.1.142"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.11.017"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-023-01301-5"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2019.1597496"}],"container-title":["Microbial Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-7915.14461","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-7915.14461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:27:51Z","timestamp":1762280871000},"score":1,"resource":{"primary":{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/10.1111\/1751-7915.14461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":59,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/1751-7915.14461"],"URL":"https:\/\/doi.org\/10.1111\/1751-7915.14461","archive":["Portico"],"relation":{},"ISSN":["1751-7915","1751-7915"],"issn-type":[{"value":"1751-7915","type":"print"},{"value":"1751-7915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2024-01-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14461"}}