{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:26:05Z","timestamp":1788222365299,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Anticancer immunotherapies have revolutionized cancer management, yet the effect of systemic anti\u2010programmed cell death protein 1 (PD\u20101) treatment is predominantly studied in tumor\u2010infiltrating lymphocytes (TILs). Its impact on PD\u20101 expressing cells in tumor\u2010draining lymph nodes (TDLNs) is not well understood and yet to be explored. Thus, further research aiming for better understanding of the PD\u20101 pathway not only in tumor tissue but also in TDLNs is warranted. In this study, we investigated the expression of PD\u20101, CD69, and HLA\u2010DR on CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells by flow cytometry analysis of peripheral blood mononuclear cells (PBMCs), TDLNs, and tumor samples from patients with oral squamous cell carcinoma (OSCC). Our data showed that both helper and cytotoxic T lymphocytes in OSCC tissue were highly activated and expressed high level of PD\u20101 (over 70% positivity). Lymphocytes in TDLNs and peripheral blood expressed significantly lower levels of PD\u20101 and other activation markers compared to TILs. Moreover, we demonstrated that a significant fraction of PD\u20101 negative TILs expressed high levels of human leukocyte antigen \u2013 DR isotype and CD69. In contrast, PD\u20101 negative cells in TDLNs and PBMCs scarcely expressed the aforementioned activation markers. Furthermore, we proved that patients with a high percentage of CD3<jats:sup>+<\/jats:sup> PD\u20101<jats:sup>+<\/jats:sup> cells in tumor\u2010draining lymph nodes had significantly lower disease\u2010free and overall survival rates (log\u2010rank test <jats:italic>P<\/jats:italic>\u00a0=\u00a0.0272 and <jats:italic>P<\/jats:italic>\u00a0=\u00a0.0276, respectively). Taken together, we proved that flow cytometry of lymph nodes in OSCC is feasible and may be used to investigate whether PD\u20101 levels in TDLNs correspond with survival and potentially with response to anti\u2010PD\u20101 therapy. Such knowledge may ultimately help guide anti\u2010PD\u20101 treatment.<\/jats:p>","DOI":"10.1111\/cas.14816","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T10:26:40Z","timestamp":1611052000000},"page":"1048-1059","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["CD4<sup>+<\/sup> and CD8<sup>+<\/sup> T cells in sentinel nodes exhibit distinct pattern of PD\u20101, CD69, and HLA\u2010DR expression compared to tumor tissue in oral squamous cell carcinoma"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-5999","authenticated-orcid":false,"given":"Krzysztof","family":"Piersiala","sequence":"first","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Sciences, Intervention and Technology Karolinska Institutet Stockholm Sweden"},{"name":"Department of Otorhinolaryngology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Farrajota Neves da Silva","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cytology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hjalmarsson","sequence":"additional","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Sciences, Intervention and Technology Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aeneas","family":"Kolev","sequence":"additional","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Sciences, Intervention and Technology Karolinska Institutet Stockholm Sweden"},{"name":"Department of Otorhinolaryngology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5sa","family":"K\u00e5gedal","sequence":"additional","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Sciences, Intervention and Technology Karolinska Institutet Stockholm Sweden"},{"name":"Department of Otorhinolaryngology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Starkhammar","sequence":"additional","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Sciences, Intervention and Technology Karolinska Institutet Stockholm Sweden"},{"name":"Department of Otorhinolaryngology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Elliot","sequence":"additional","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Sciences, Intervention and Technology Karolinska Institutet Stockholm Sweden"},{"name":"Medical Unit Head Neck, Lung and Skin Cancer Karolinska University Hospital Stokcholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Marklund","sequence":"additional","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Sciences, Intervention and Technology Karolinska Institutet Stockholm Sweden"},{"name":"Department of Otorhinolaryngology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregori","family":"Margolin","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Karolinska University Hospital Stockholm Sweden"},{"name":"Medical Unit Head Neck, Lung and Skin Cancer Karolinska University Hospital Stokcholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Munck\u2010Wikland","sequence":"additional","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Sciences, Intervention and Technology Karolinska Institutet Stockholm Sweden"},{"name":"Medical Unit Head Neck, Lung and Skin Cancer Karolinska University Hospital Stokcholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Kumlien Geor\u00e9n","sequence":"additional","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Sciences, Intervention and Technology Karolinska Institutet Stockholm Sweden"},{"name":"Department of Otorhinolaryngology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars\u2010Olaf","family":"Cardell","sequence":"additional","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Sciences, Intervention and Technology Karolinska Institutet Stockholm Sweden"},{"name":"Department of Otorhinolaryngology Karolinska University Hospital Stockholm 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