{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:55:24Z","timestamp":1790906124024,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172848"],"award-info":[{"award-number":["82172848"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with non\u2010small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal\u2010associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD\u2010associated NSCLC and their involvement in the immune response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Flow cytometry, immunohistochemistry, and immunofluorescence were performed on tissue samples of patients with NSCLC, with or without COPD, treated with or without anti\u2010programmed death 1 (PD1) immunotherapy. MAIT cells were stimulated with 5\u2010OP\u2010RU using a mouse subcutaneous tumor model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Tumors contained significantly more MAIT cells than paraneoplastic tissues, and CD8<jats:sup>+<\/jats:sup> MAIT cells accounted for more than 90% of these cells. Patients with NSCLC and COPD had higher CD8<jats:sup>+<\/jats:sup> MAIT cell counts than those with NSCLC without COPD. Additionally, patients with NSCLC and COPD displayed reduced expression of the activation marker, CD69, and functional markers, granzyme B (GZMB) and interferon \u03b3 (IFN\u03b3), and higher expression of the immune exhaustion marker, PD1. Among patients who received immunotherapy, the proportion with a complete or partial response was higher in those with COPD than in those without COPD. In patients with NSCLC and COPD, the major pathologic response (MPR) group had higher MAIT levels than those in the no major pathologic response (NPR) group. In the mouse subcutaneous tumor model stimulation of MAIT cells using 5\u2010OP\u2010RU enhanced the antitumor effects of anti\u2010PD1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In patients with NSCLC and COPD, response to immunotherapy is associated with accumulation of CD8<jats:sup>+<\/jats:sup> MAIT cells showing immune exhaustion. These findings may contribute to innovative approaches for immunotherapy targeting CD8<jats:sup>+<\/jats:sup> MAIT cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.7112","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T07:06:12Z","timestamp":1711004772000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>MAIT<\/scp> cells are associated with responsiveness to neoadjuvant immunotherapy in <scp>COPD<\/scp>\u2010associated <scp>NSCLC<\/scp>"],"prefix":"10.1002","volume":"13","author":[{"given":"Yanze","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abudumijiti","family":"Abuduwayiti","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyun","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gening","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4316-4243","authenticated-orcid":false,"given":"Jie","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21708"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01260-z"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD013343.pub2"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201704-0795OC"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100039"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.09.009"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0444-8"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0191-y"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2022-0131OC"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abc8188"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-20-0925"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-21-0058"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1283"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15094"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25009-4"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0569"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.07.026"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-022-02045-2"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01597"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22130-1"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2019.03.027"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201706-1110OC"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32235"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005902"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.7112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T05:21:53Z","timestamp":1726723313000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.7112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":24,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/cam4.7112"],"URL":"https:\/\/doi.org\/10.1002\/cam4.7112","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2023-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e7112"}}