{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:29:15Z","timestamp":1787077755144,"version":"build-2736575974"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"34","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015127","name":"Commonwealth Foundation for Cancer Research Foundation","doi-asserted-by":"publisher","award":["Commonwealth"],"award-info":[{"award-number":["Commonwealth"]}],"id":[{"id":"10.13039\/100015127","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013041","name":"JHU | Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University | Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","doi-asserted-by":"publisher","award":["BKI"],"award-info":[{"award-number":["BKI"]}],"id":[{"id":"10.13039\/100013041","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":[[2026,8,25]]},"abstract":"<jats:p>\n                    Mucosal-associated invariant T (MAIT) cells are innate-like T cells capable of MR1-dependent immune surveillance, but how intratumoral bacteria modulate MR1 expression in human lung tumors remains unclear. We studied intratumoral MAIT cells from paired single-cell RNA and TCR sequencing datasets of tumor-infiltrating CD3 T cells isolated from non-small cell lung cancer tumors in patients receiving neoadjuvant PD-1 blockade therapy. MAIT cells were subclustered to identify conventional MAIT-associated TCR clonotypes, which were then used to examine how bacterial exposure impacts cell-surface MR1 expression and downstream MAIT TCR activation. We found that select intratumoral\n                    <jats:italic toggle=\"yes\">Enterococcus<\/jats:italic>\n                    species (spp.) did not directly activate MAIT cells but enhanced MR1-dependent MAIT activation in the presence of exogenous 5-OP-RU by increasing cell-surface MR1 expression on antigen-presenting cells including dendritic cells, B cells, and mononuclear phagocytes. This increase in MR1 cell surface expression is modulated through a posttranscriptional mechanism consistent with altered intracellular processing and trafficking of MR1. These findings reveal a role for tumor-associated bacteria in modulating MR1-dependent innate-like T cell activation and provide a basis for future studies examining whether this process influences response to immune checkpoint blockade.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2617943123","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:59:27Z","timestamp":1787075967000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Select intratumoral riboflavin-auxotrophic\n                    <i>Enterococcus<\/i>\n                    species enhance cell surface MR1 expression and MAIT TCR activation in lung cancer"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7252-5717","authenticated-orcid":false,"given":"Pakhi","family":"Birla","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lansaol","family":"Yang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanting","family":"Shan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6204-7413","authenticated-orcid":false,"given":"Sakura","family":"Minamisawa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01692sz90","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Oncology, Faculty of Medicine, Juntendo University","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omkar","family":"Dhaygude","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haritha","family":"Manoj","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1825-2439","authenticated-orcid":false,"given":"Alex J.","family":"Lee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4340-6936","authenticated-orcid":false,"given":"Jacqueline","family":"Ferri","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4107-6752","authenticated-orcid":false,"given":"Ying","family":"Zheng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5118-1217","authenticated-orcid":false,"given":"Andrew","family":"Northcutt","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongni","family":"Fan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadley","family":"Beauregard","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Division of Infectious Disease, Johns Hopkins University","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3443-0637","authenticated-orcid":false,"given":"Zhen","family":"Zeng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kellie N.","family":"Smith","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7839-8483","authenticated-orcid":false,"given":"Fyza Y.","family":"Shaikh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4059-1661","authenticated-orcid":false,"given":"Cynthia L.","family":"Sears","sequence":"additional","affiliation":[{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]},{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Division of Infectious Disease, Johns Hopkins University","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6215-1013","authenticated-orcid":false,"given":"Drew M.","family":"Pardoll","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-3953","authenticated-orcid":false,"given":"Franck","family":"Housseau","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","place":["Baltimore"]},{"name":"Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20232298"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax6624"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003681"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1890"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20231487"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130958"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10198-w"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13160"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0578-8"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI181895"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.12.005"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.ade6924"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3679"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.24476"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2414792121"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12506"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adn0126"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.07.026"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03752-4"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-024-03046-3"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005902"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25322-y"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140484"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.570828"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3142"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11605"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501087200"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3416"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2017.11.028"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2014.02.003"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-80160-4"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12639"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2400781121"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-18-1343"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010434"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12556"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2022.100818"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-025-01211-7"},{"key":"e_1_3_4_39_2","article-title":"MR1 overexpression correlates with poor clinical prognosis in glioma patients","volume":"3","author":"Kubica P.","year":"2021","unstructured":"P. Kubica , MR1 overexpression correlates with poor clinical prognosis in glioma patients. Neurooncol. Adv. 3, vdab034 (2021).","journal-title":"Neurooncol. Adv."},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21928-4"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc9113"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-017-0040-3"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1891-0"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3589"},{"key":"e_1_3_4_45_2","unstructured":"P. Birla pbirla1\/MAIT_NSCLC_enterococcus. Zenodo. https:\/\/doi.org\/10.5281\/zenodo.21795870. Deposited 4 August 2026."},{"key":"e_1_3_4_46_2","unstructured":"P. Birla pbirla1\/jhmi-sears-pakhi-wgs-microbiome. Zenodo. https:\/\/doi.org\/10.5281\/zenodo.21795884. Deposited 4 August 2026."},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","unstructured":"P. Birla Synergistic role of riboflavin-auxotrophic Enterococcus for MR1 expression and in-tra-tumoral mucosal associated invariant T (MAIT) cell activation. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE320009. Deposited 23 February 2026.","DOI":"10.1101\/2025.11.25.690539"},{"key":"e_1_3_4_48_2","unstructured":"P. Birla Lung FFPE microbiome sequencing. Sequence Read Archive. https:\/\/www.ncbi.nlm.nih.gov\/bioproject?term=PRJNA1425760. Deposited 19 February 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2617943123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:59:47Z","timestamp":1787075987000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2617943123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":48,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2026,8,25]]}},"alternative-id":["10.1073\/pnas.2617943123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2617943123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"assertion":[{"value":"2026-06-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2617943123"}}