{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:05:38Z","timestamp":1790172338460,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203226"],"award-info":[{"award-number":["82203226"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303602"],"award-info":[{"award-number":["82303602"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404002"],"award-info":[{"award-number":["82404002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M721410"],"award-info":[{"award-number":["2022M721410"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Bacteria in tumors are increasingly recognized to be a part of the tumor microenvironment and their biological function depends on the location and relative abundance of a given microorganism or microbial community. Genetic sequencing data directly from tissue samples to detection of active metabolic signals from microorganisms, cell\u2010microbiome interactions, ultrastructural localization of microorganisms; these are all different kinds of inferences about the functional role of the microbiome, and the evidence for \u201cmicrobial presence and function\u201d grows in a stepwise fashion. Furthermore, most current microbial detection methods do not, alone, predict the viability, biological activity, or functional properties of microorganisms. In this review, we compare different existing microbial detection techniques and distinguish three spatial paradigms: organized communities in tissue, intracellular bacteria, and extracellular bacteria. We summarize how each paradigm influences signal transduction, metabolism, metastatic spread, treatment resistance, antitumor immunity, and immunotherapy responses. We focus on low\u2010biomass contamination, batch effects, negative controls, absolute quantification, and orthogonal validation. Finally, we classify results according to localization, biological role, clinical evidence, application, and applications, while distinguishing observations of human patients from mechanistic and therapeutic preclinical studies. Spatial microbiology provides useful information about tumor\u2010microbial interactions, but clinically actionable conclusions require standard analysis, reproducible localization, viability or activity, and functional disruption experiments to demonstrate microbial effects and independent clinical validation.<\/jats:p>","DOI":"10.1111\/cas.70536","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T06:30:41Z","timestamp":1789367441000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in Spatial Heterogeneity and Cellular Localization Specificity of Intratumoral Bacteria"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2382-8612","authenticated-orcid":false,"given":"Minlan","family":"Ren","sequence":"first","affiliation":[{"name":"Department of General Surgery The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research  Nanjing Jiangsu China"},{"name":"Medical Center for Digestive Diseases The Second Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jia","sequence":"additional","affiliation":[{"name":"Medical Center for Digestive Diseases The Second Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Center for Digestive Diseases The Second Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Center for Digestive Diseases The Second Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanxiang","family":"Shen","sequence":"additional","affiliation":[{"name":"Medical Center for Digestive Diseases The Second Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0959-7689","authenticated-orcid":false,"given":"Yun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangli","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanying","family":"Xiong","sequence":"additional","affiliation":[{"name":"Medical Center for Digestive Diseases The Second Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7247-5289","authenticated-orcid":false,"given":"Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,13]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01693-0"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.016"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay9189"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.03.021"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05435-0"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.01.004"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.12.044"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ads6335"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2024.01.007"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-025-01165-5"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0041-0"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.23053"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01678-9"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-63414-1"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2018.11.003"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-025-02035-2"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2026098"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens15070687"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202400694"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70273"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008982"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2014.12.014"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1165790"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.09.010"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adj7402"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.02.027"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2421710122"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-004698"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-024-00746-0"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-24-2580"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2022.2156255"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01890-9"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1331"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.09.009"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101397"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-321187"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.08.019"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal5240"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03368-8"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.09.005"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-023-01483-0"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02335-3"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202405331"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2026.108902"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.02.009"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-025-01067-1"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iotech.2025.101066"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-024-01654-2"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.21987"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-25-4420"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.70080"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.07.008"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-0201"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.add9667"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202503523"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.engmic.2022.100034"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01957-8"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202401538"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2024.06.016"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.20.1.142"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-2065"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-0118"},{"key":"e_1_2_14_64_1","first-page":"1","article-title":"Bacterial Engineering for Cancer Therapy","author":"Chen N.","year":"2026","journal-title":"Nature Cancer"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202102580"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101512"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202417920"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000003807"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.5c00786"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adu8000"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2026.102681"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01918-0"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70536","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.70536","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70536","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:26:52Z","timestamp":1790170012000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,13]]},"references-count":71,"alternative-id":["10.1111\/cas.70536"],"URL":"https:\/\/doi.org\/10.1111\/cas.70536","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,13]]},"assertion":[{"value":"2026-05-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cas.70536"}}