{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T15:10:10Z","timestamp":1743865810516,"version":"3.40.3"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071856","81671579","82103316"],"award-info":[{"award-number":["82071856","81671579","82103316"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0113101"],"award-info":[{"award-number":["2020YFA0113101"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2025,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Radiotherapy (RT) is a commonly used clinical management for hypopharyngeal squamous cell carcinoma (HPSCC), which represents the most unfavorable prognosis among all subtypes of head and neck squamous cell carcinoma. However, radiation may cause lymphopenia, a significantly adverse event with detrimental prognostic implications for patients. While CD8<jats:sup>+<\/jats:sup> T cells are vital in tumor immunity, the specific effects of RT on CD8<jats:sup>+<\/jats:sup> T cells as well as the underlying mechanisms have not been clearly elucidated. Here we found that subpopulations of peripheral T lymphocytes exhibited differential profiles in patients with HPSCC compared to healthy individuals both pre\u2010 and post\u2010irradiation. Importantly, CD8<jats:sup>+<\/jats:sup> T cells from HPSCC patients showed greater reduction of cytokine production, more severe proliferation defect, and increased apoptosis compared to those from healthy individuals after in vitro irradiation. Mechanistically, the ATM\u2010Chk2 pathway mediated the enhanced apoptosis of CD8<jats:sup>+<\/jats:sup> T lymphocytes from HPSCC patients upon irradiation. Therefore, our study demonstrated that CD8<jats:sup>+<\/jats:sup> T cells in patients with HPSCC exhibit a higher susceptibility to radiation\u2010induced damage compared to those in healthy individuals. The ATM\u2010Chk2 pathway represents a potential immunotherapeutic target for safeguarding CD8<jats:sup>+<\/jats:sup> T cells in HPSCC patients against radiation\u2010induced apoptosis.<\/jats:p>","DOI":"10.1002\/ijc.35329","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T13:53:41Z","timestamp":1738936421000},"page":"2010-2023","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>CD8<\/scp><sup>+<\/sup> T cells in patients with hypopharyngeal squamous cell carcinoma are susceptible to radiation\u2010induced damage"],"prefix":"10.1002","volume":"156","author":[{"given":"Hanqing","family":"Lin","sequence":"first","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai China"},{"name":"Department of Otorhinolaryngology, Fujian Institute of Otorhinolaryngology The First Affiliated Hospital of Fujian Medical University  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0207-8015","authenticated-orcid":false,"given":"Jingyu","family":"Ma","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5625-8324","authenticated-orcid":false,"given":"Yu","family":"Heng","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3543-9668","authenticated-orcid":false,"given":"Xiaoke","family":"Zhu","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuyan","family":"Jin","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuping","family":"Ding","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology, Department of Immunology and Microbiology Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Tao","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liming","family":"Lu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology, Department of Immunology and Microbiology Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2018.09.025"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2019.09.005"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2020.01.102"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.4115"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2020.0031"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15618"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052494"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032542"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2820"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200563"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.5.3099"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-14-1015"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.08.047"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2021.01.034"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2021.07.1695"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602252"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31999-8"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad7118"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00290"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.annonc.2020.08.2268","article-title":"LBA38 Pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced head and neck squamous cell carcinoma (LA\u2010HNSCC): results of the GORTEC 2015\u201001 \u201cPembroRad\u201d randomized trial","volume":"31","author":"Bourhis J","year":"2020","journal-title":"Ann Oncol"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30737-3"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms16073"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.022"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2020.01.032"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2018.09.010"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2021.103226"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002371-200307000-00005"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1255"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.2307\/3577549"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.05.015"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-380888-2.00003-0"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canrad.2022.08.008"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/coa.14160"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13311"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2307\/3578787"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400434"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.648652"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2014.04.009"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/HP.0000000000001615"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553002.2018.1408976"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553000600930699"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.05.121"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1095-7"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443034"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.04.011"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.35329","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T14:56:35Z","timestamp":1743864995000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.35329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,7]]},"references-count":45,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,5,15]]}},"alternative-id":["10.1002\/ijc.35329"],"URL":"https:\/\/doi.org\/10.1002\/ijc.35329","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"type":"print","value":"0020-7136"},{"type":"electronic","value":"1097-0215"}],"subject":[],"published":{"date-parts":[[2025,2,7]]},"assertion":[{"value":"2024-08-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}