{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:12:33Z","timestamp":1753891953445,"version":"3.41.2"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>In an immune-competent context nivolumab showed long-term benefit in overall survival in recurrent\/metastatic head and neck squamous cell carcinoma (HNSCC); however, in special cancer population such as these patients with immunodeficiency and viral infections, data on checkpoint inhibitors (ICI) activity are scant. Herein, we report a patient with a Human papilloma virus (HPV)-related oropharyngeal cancer (OPC) and CD4 lymphocytopenia. After a first-line treatment complete remission, the patient experienced Human Polyomavirus (JCV) infection in the brain. Consequently, to the recovery from progressive multifocal leukoencephalopathy (PML) the patient metastasized and was enrolled in a single-arm trial with nivolumab (EudraCT number: 2017-000562-30). A complete and durable response (more 3 years) was observed after 10 nivolumab injections Q2wks, interrupted for persistent drug related G2 diarrhea and a syndrome of inappropriate antidiuretic hormone secretion. We describe the circulating immune profile (before-, during-, and after nivolumab), consistent with the clinical history. Moreover, during nivolumab treatment, brain MRI evidenced the presence of small punctuate areas of contrast enhancement, reflecting a mild immune response in perivascular spaces. By cytofluorimetry, we observed that during JCV infection the CD4\/CD8 ratio of the patient was under the normal values. After JCV infection recovery and before nivolumab treatment, CD4\/CD8 ratio reached the normality threshold, even if the CD4<jats:sup>+<\/jats:sup> T cell count remained largely under the normal values. During ICI, gene expression xCell analyses of circulating immune cells of the patient, showed a progressive normalization of the total immune profile, with significant boost in CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells and a reduction in NK T, comparable to the circulating immune profile of reference tumor-free HNSCC patients. The present case supports the activity of ICI in a population of special cancer patients; whether JCV and HPV infections (alone or together) might have a possible role as immune booster(s), require further investigations.<\/jats:p>","DOI":"10.3389\/fonc.2021.799453","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T04:14:29Z","timestamp":1641788069000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Complete Response to Nivolumab in Recurrent\/Metastatic HPV-Positive Head and Neck Squamous Cell Carcinoma Patient After Progressive Multifocal Leukoencephalopathy: A Case Report"],"prefix":"10.3389","volume":"11","author":[{"given":"Laura Deborah","family":"Locati","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara Serena","family":"Serafini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Carenzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvana","family":"Canevari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Perrone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ester","family":"Orlandi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Delbue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Cavalieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Berzeri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Pichiecchio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa Francesca","family":"Licitra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Marchioni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loris","family":"De Cecco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.oraloncology.2018.04.008","article-title":"Nivolumab vs Investigator\u2019s Choice in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: 2-Year Long-Term Survival Update of CheckMate 141 With Analyses by Tumor PD-L1 Expression","volume":"81","author":"Ferris","year":"2018","journal-title":"Oral Oncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"101977","DOI":"10.1016\/j.ctrv.2020.101977","article-title":"Biomarkers for Immunotherapy Response in Head and Neck Cancer","volume":"84","author":"Gavrielatou","year":"2020","journal-title":"Cancer Treat Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30642","article-title":"Immune Checkpoint Inhibitors in Challenging Populations","volume":"123","author":"Johnson","year":"2017","journal-title":"Cancer"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.21037\/atm-20-5207","article-title":"Considerations for Immunotherapy in Patients With Cancer and Comorbid Immune Dysfunction","volume":"9","author":"Florou","year":"2021","journal-title":"Ann Transl Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21388","article-title":"The Eighth Edition AJCC Cancer Staging Manual: Continuing to Build a Bridge From a Population-Based to a More \u201cPersonalized\u201d Approach to Cancer Staging","volume":"67","author":"Amin","year":"2017","journal-title":"CA Cancer J Clin"},{"key":"B7","doi-asserted-by":"publisher","first-page":"922","DOI":"10.3390\/cancers12040922","article-title":"Tumor Biomarkers for the Prediction of Distant Metastasis in Head and Neck Squamous Cell Carcinoma","volume":"12","author":"Alfieri","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000258355.23810.c6","article-title":"Outcomes Validity and Reliability of the Modified Rankin Scale: Implications for Stroke Clinical Trials - 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