{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T09:49:12Z","timestamp":1792403352687,"version":"4.4.0"},"reference-count":35,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"28","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>The impact of the intratumoral microbiome on immune checkpoint inhibitor (ICI) efficacy in patients with non\u2013small-cell lung cancer (NSCLC) is unknown. Preclinically, intratumoral Escherichia is associated with a proinflammatory tumor microenvironment and decreased metastases. We sought to determine whether intratumoral Escherichia is associated with outcome to ICI in patients with NSCLC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>We examined the intratumoral microbiome in 958 patients with advanced NSCLC treated with ICI by querying unmapped next-generation sequencing reads against a bacterial genome database. Putative environmental contaminants were filtered using no-template controls (n = 2,378). The impact of intratumoral Escherichia detection on overall survival (OS) was assessed using univariable and multivariable analyses. The findings were further validated in an external independent cohort of 772 patients. Escherichia fluorescence in situ hybridization (FISH) and transcriptomic profiling were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In the discovery cohort, read mapping to intratumoral Escherichia was associated with significantly longer OS (16\n                      <jats:italic>v<\/jats:italic>\n                      11 months; hazard ratio, 0.73 [95% CI, 0.59 to 0.92];\n                      <jats:italic>P<\/jats:italic>\n                      = .0065) in patients treated with single-agent ICI, but not combination chemoimmunotherapy. The association with OS in the single-agent ICI cohort remained statistically significant in multivariable analysis adjusting for prognostic features including PD-L1 expression (\n                      <jats:italic>P<\/jats:italic>\n                      = .023). Analysis of an external validation cohort confirmed the association with improved OS in univariable and multivariable analyses of patients treated with single-agent ICI, and not in patients treated with chemoimmunotherapy. Escherichia localization within tumor cells was supported by coregistration of FISH staining and serial hematoxylin and eosin sections. Transcriptomic analysis correlated Escherichia-positive samples with expression signatures of immune cell infiltration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Read mapping to potential intratumoral Escherichia was associated with survival to single-agent ICI in two independent cohorts of patients with NSCLC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.23.01488","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T16:01:55Z","timestamp":1721664115000},"page":"3339-3349","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":41,"title":["Intratumoral Escherichia Is Associated With Improved Survival to Single-Agent Immune Checkpoint Inhibition in Patients With Advanced Non\u2013Small-Cell Lung Cancer"],"prefix":"10.1200","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1981-1535","authenticated-orcid":false,"given":"Arielle","family":"Elkrief","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9155-556X","authenticated-orcid":false,"given":"Meagan","family":"Montesion","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7790-5615","authenticated-orcid":false,"given":"Smruthy","family":"Sivakumar","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2860-0994","authenticated-orcid":false,"given":"Caryn","family":"Hale","sequence":"additional","affiliation":[{"name":"Marie-Jos\u00e9e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8651-5317","authenticated-orcid":false,"given":"Anita S.","family":"Bowman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1432-9056","authenticated-orcid":false,"given":"Ayy\u00fcce","family":"Beg\u00fcm Bekta\u015f","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Bradic","sequence":"additional","affiliation":[{"name":"Marie-Jos\u00e9e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfei","family":"Kang","sequence":"additional","affiliation":[{"name":"Molecular Cytology Core, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2835-3994","authenticated-orcid":false,"given":"Eric","family":"Chan","sequence":"additional","affiliation":[{"name":"Molecular Cytology Core, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7831-5550","authenticated-orcid":false,"given":"Pooja","family":"Gogia","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, West Virginia University School of Medicine, West Virginia University Institute, Morgantown, WV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Manova-Todorova","sequence":"additional","affiliation":[{"name":"Molecular Cytology Core, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Mata","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacklynn V.","family":"Egger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hira","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas D.","family":"Socci","sequence":"additional","affiliation":[{"name":"Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4961-8219","authenticated-orcid":false,"given":"Daniel W.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Informatics Systems, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Rosiek","sequence":"additional","affiliation":[{"name":"Molecular Cytology Core, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanli","family":"Meng","sequence":"additional","affiliation":[{"name":"Marie-Jos\u00e9e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grittney","family":"Tam","sequence":"additional","affiliation":[{"name":"Marie-Jos\u00e9e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Fan","sequence":"additional","affiliation":[{"name":"Molecular Cytology Core, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-9061","authenticated-orcid":false,"given":"Alexander","family":"Drilon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Department of Medicine, Weill Cornell, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0377-9510","authenticated-orcid":false,"given":"Helena A.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Department of Medicine, Weill Cornell, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5357-4313","authenticated-orcid":false,"given":"Gregory J.","family":"Riely","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Department of Medicine, Weill Cornell, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5801-3144","authenticated-orcid":false,"given":"Natasha","family":"Rekhtman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7234-3446","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Quintanal Villalonga","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4905-8946","authenticated-orcid":false,"given":"Snjezana","family":"Dogan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6656-1239","authenticated-orcid":false,"given":"Umesh","family":"Bhanot","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Precision Pathology Center, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-8477","authenticated-orcid":false,"given":"Mithat","family":"G\u00f6nen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1863-1199","authenticated-orcid":false,"given":"Brian","family":"Loomis","sequence":"additional","affiliation":[{"name":"Marie-Jos\u00e9e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2670-9777","authenticated-orcid":false,"given":"Matthew D.","family":"Hellmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Department of Medicine, Weill Cornell, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-1416","authenticated-orcid":false,"given":"Adam J.","family":"Schoenfeld","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9055-7213","authenticated-orcid":false,"given":"Marc","family":"Ladanyi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5204-3465","authenticated-orcid":false,"given":"Charles M.","family":"Rudin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Department of Medicine, Weill Cornell, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-0237","authenticated-orcid":false,"given":"Chad M.","family":"Vanderbilt","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_9_2_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1059"},{"key":"e_1_3_9_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan3706"},{"key":"e_1_3_9_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01655-5"},{"key":"e_1_3_9_5_2","first-page":"1775","article-title":"Lung tissue microbial profile in lung cancer is distinct from emphysema","volume":"8","author":"Liu Y","year":"2018","unstructured":"Liu Y, O'Brien JL, Ajami NJ, et al: Lung tissue microbial profile in lung cancer is distinct from emphysema. Am J Cancer Res 8:1775-1787, 2018","journal-title":"Am J Cancer Res"},{"key":"e_1_3_9_6_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00062212"},{"key":"e_1_3_9_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.31"},{"key":"e_1_3_9_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/2049-2618-1-19"},{"key":"e_1_3_9_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0263"},{"key":"e_1_3_9_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay9189"},{"key":"e_1_3_9_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.09.009"},{"key":"e_1_3_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.08.090"},{"key":"e_1_3_9_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-0201"},{"key":"e_1_3_9_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2014.12.006"},{"key":"e_1_3_9_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0264138"},{"key":"e_1_3_9_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.3241"},{"key":"e_1_3_9_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2014.12.006"},{"key":"e_1_3_9_18_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.9052"},{"key":"e_1_3_9_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-006994"},{"key":"e_1_3_9_20_2","doi-asserted-by":"publisher","DOI":"10.32614\/RJ-2021-053"},{"key":"e_1_3_9_21_2","unstructured":"Vanderbilt CM: Intratumoral microbiome analysis code. https:\/\/github.com\/chadvanderbilt\/ITMIO"},{"key":"e_1_3_9_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100891"},{"key":"e_1_3_9_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06498-3"},{"key":"e_1_3_9_24_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0272OC"},{"key":"e_1_3_9_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00333"},{"key":"e_1_3_9_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0382-x"},{"key":"e_1_3_9_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abi6899"},{"key":"e_1_3_9_28_2","unstructured":"Dykema AG Zhang J Zhang B et al: Lung tumor-infiltrating Treg have divergent transcriptional profiles and function linked to checkpoint blockade response. bioRxiv 10.1101\/2022.12.13.520329"},{"key":"e_1_3_9_29_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-20-0969"},{"key":"e_1_3_9_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00057"},{"key":"e_1_3_9_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00421-2"},{"key":"e_1_3_9_32_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-19-0608"},{"key":"e_1_3_9_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202200030"},{"key":"e_1_3_9_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.295"},{"key":"e_1_3_9_35_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-0201"},{"key":"e_1_3_9_36_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00062212"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.23.01488","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T17:59:38Z","timestamp":1727373578000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.23.01488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":35,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1200\/JCO.23.01488"],"URL":"https:\/\/doi.org\/10.1200\/jco.23.01488","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2023-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-12","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}