{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T21:01:44Z","timestamp":1771880504915,"version":"3.50.1"},"reference-count":17,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T00:00:00Z","timestamp":1689984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP21K09664"],"award-info":[{"award-number":["JP21K09664"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Neck dissection for cervical lymph node metastasis is an established procedure for head and neck cancer (HNC). However, with the advent of immunotherapy, head and neck surgical oncologists need to rethink removing all lymph nodes, including those with immune function. We investigated the anti-cancer immune response of the cervical lymph nodes in four patients with human papillomavirus type 16 (HPV16)-positive head and neck squamous cell carcinoma. Using lymphocytes extracted from local, metastatic, and non-metastatic lymph nodes and peripheral blood from these patients, we performed an intracellular flow cytometric cytokine assay using anti-IFN\u03b3 and anti-TNF-\u03b1 monoclonal antibodies to detect HPV16 E6- and E7-specific T cells. HPV status and p16 immunostaining were determined by in situ detection using the HPV RNAscope method and immunohistochemistry. In one case, E6-specific and E7-specific CD8+ T cells were detected in proximal metastatic nodes and distal non-metastatic nodes. This finding suggests that non-metastatic nodes should be preserved for their immune function during neck dissection and that the immune function of non-metastatic lymph nodes is important when administering immunotherapy. In this context, head and neck surgical oncologists treating HNC should consider the place of immunotherapy and neck dissection in the treatment of HNC.<\/jats:p>","DOI":"10.3390\/jpm13071174","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:47:03Z","timestamp":1690159623000},"page":"1174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Immune Status of Cervical Lymph Nodes in Head and Neck Cancer\u2014A Surgical Oncology Perspective"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0931-6821","authenticated-orcid":false,"given":"Hiromu","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4093-9533","authenticated-orcid":false,"given":"Tetsuya","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunpei","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6642-6763","authenticated-orcid":false,"given":"Daisuke","family":"Inukai","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Maruo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taishi","family":"Takahara","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Satou","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4855-4366","authenticated-orcid":false,"given":"Toyonori","family":"Tsuzuki","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1466-8824","authenticated-orcid":false,"given":"Susumu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Research Creation Support Center, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuzo","family":"Ueda","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences, Department of Physiological Science, Nagoya University Graduate School of Medicine, Furo-cho, Chikusa-ku, Nagoya-shi 464-8601, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6044-686X","authenticated-orcid":false,"given":"Yasushi","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.soc.2015.03.001","article-title":"Epidemiology of head and neck cancer","volume":"24","author":"Rettig","year":"2015","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1001\/jama.1987.03400220086043","article-title":"Landmark article Dec. 1, 1906: Excision of cancer of the head and neck. With special reference to the plan of dissection based on one hundred and thirty-two operations. By George Crile","volume":"258","author":"Crile","year":"1987","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1002\/1097-0142(195105)4:3<441::AID-CNCR2820040303>3.0.CO;2-O","article-title":"Neck dissection","volume":"4","author":"Martin","year":"1951","journal-title":"Cancer"},{"key":"ref_4","first-page":"49755","article-title":"The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June, 1889, to January, 1894","volume":"20","author":"Halstead","year":"1894","journal-title":"Ann. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1007\/s00405-012-2153-x","article-title":"The evolving role of selective neck dissection for head and neck squamous cell carcinoma","volume":"270","author":"Robbins","year":"2013","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1056\/NEJMoa1602252","article-title":"Nivolumab for recurrent squamous-cell carcinoma of the head and neck","volume":"375","author":"Ferris","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0140-6736(18)31999-8","article-title":"Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): A randomized, open-label, phase 3 study","volume":"393","author":"Cohen","year":"2019","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","article-title":"Oncology meets immunology: The cancer-immunity cycle","volume":"39","author":"Chen","year":"2013","journal-title":"Immunity"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4298","DOI":"10.1038\/s41467-022-31941-w","article-title":"Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC","volume":"13","author":"Faraji","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pe\u0161ut, E., \u0110uki\u0107, A., Luli\u0107, L., Skelin, J., \u0160imi\u0107, I., Milutin Ga\u0161perov, N., Tomai\u0107, V., Sabol, I., and Grce, M. (2021). Human papillomaviruses-associated cancers: An update of current knowledge. Viruses, 13.","DOI":"10.3390\/v13112234"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1002\/ijc.22464","article-title":"HPV integration begins in the tonsillar crypt and leads to the alteration of p16, EGFR and c-myc during tumor formation","volume":"120","author":"Kim","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41586-021-03862-z","article-title":"Functional HPV-specific PD-1(+) stem-like CD8 T cells in head and neck cancer","volume":"597","author":"Eberhardt","year":"2021","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"749398","DOI":"10.3389\/fonc.2021.749398","article-title":"A tumor-infiltration CD8+ T cell-based gene signature for facilitating the prognosis and estimation of immunization responses in HPV+ head and neck squamous cell cancer","volume":"11","author":"Wu","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e20200389","DOI":"10.1084\/jem.20200389","article-title":"Profiling HPV-16-specific T cell responses reveals broad antigen reactivities in oropharyngeal cancer patients","volume":"217","author":"Bhatt","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6159","DOI":"10.1158\/0008-5472.CAN-18-0163","article-title":"Human papilloma virus specific immunogenicity and dysfunction of CD8(+) T cells in head and neck cancer","volume":"78","author":"Krishna","year":"2018","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/S0140-6736(19)32591-7","article-title":"Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): A randomised, open-label, phase 3 study","volume":"394","author":"Burtness","year":"2019","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e124507","DOI":"10.1172\/jci.insight.124507","article-title":"Tumor-draining lymph nodes are pivotal in PD-1\/PD-L1 checkpoint therapy","volume":"3","author":"Fransen","year":"2018","journal-title":"JCI Insight"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/7\/1174\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:17:19Z","timestamp":1760127439000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/7\/1174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,22]]},"references-count":17,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["jpm13071174"],"URL":"https:\/\/doi.org\/10.3390\/jpm13071174","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,22]]}}}