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CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma

Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OSCC) are clinical and biological distinct from their HPV-unrelated counterparts. Patients with HPV-related OSCC display improved prognosis and therefore we investigated possible immune cell infiltrations associated with t...

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Main Authors: Wagner, Steffen (Author) , Wittekindt, Claus (Author) , Reuschenbach, Miriam (Author) , Hennig, Ben (Author) , Thevarajah, Mauran (Author) , Würdemann, Nora (Author) , Prigge, Elena-Sophie (Author) , Knebel Doeberitz, Magnus von (Author) , Dreyer, Thomas (Author) , Gattenlöhner, Stefan (Author) , Klussmann, Jens Peter (Author)
Format: Article (Journal)
Language:English
Published: [2016]
In: International journal of cancer
Year: 2015, Volume: 138, Issue: 9, Pages: 2263-2273
ISSN:1097-0215
DOI:10.1002/ijc.29962
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/ijc.29962
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.29962
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Author Notes:Steffen Wagner, Claus Wittekindt, Miriam Reuschenbach, Ben Hennig, Mauran Thevarajah, Nora Würdemann, Elena-Sophie Prigge, Magnus von Knebel Doeberitz, Thomas Dreyer, Stefan Gattenlöhner and Jens Peter Klussmann
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Summary:Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OSCC) are clinical and biological distinct from their HPV-unrelated counterparts. Patients with HPV-related OSCC display improved prognosis and therefore we investigated possible immune cell infiltrations associated with this tumor phenotype. We retrospectively analyzed a randomly selected cohort of 140 OSCC for presence of immune cells and HPV by immunohistochemistry and PCR followed by bead-based hybridization (Luminex technology). HPV prevalence was 24.3% as determined by positive staining of p16INK4a and detection of high risk HPV-DNA. We found significantly higher numbers of CD56 positive (CD56+) cells in tumor and surrounding microenvironment in HPV-associated compared to HPV-negative OSCC (t-test: p = 0.004 and p = 0.002). For the entire cohort presence of CD56+ cells was associated with increased overall survival independent from HPV (Kaplan-Meier: p = 0.002; Cox regression: p = 0.042). Presence of CD56+ cells also correlated with a better outcome in HPV-negative and especially in HPV-negative OSCC with alcohol consumption ≤2 standard drinks per day (Kaplan-Meier: p = 0.05 and p = 0.003). Immunofluorescence localization of granular Granzyme B (GZMB) within CD56+ cells and coexpression of CD16 and CD56 suggests that detected CD56+ cells mainly represent cytotoxic Natural Killer (NK) cells. The fraction of potentially cytotoxic NK cells was significantly higher in HPV-associated compared to HPV-negative OSCC (Mann-Whitney-U-Test: p = 0.011). The elevated abundance and activity of cytotoxic NK cells in OSCC with HPV driven carcinogenesis might contribute to favorable outcome in HPV-related OSCC.
Item Description:Online 13 Dec 2015
Gesehen am 05.06.2020
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.29962

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