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Titel: The HPV and p63 Status in Penile Cancer Are Linked with the Infiltration and Therapeutic Availability of Neutrophils
VerfasserIn: Bernhard, Muriel Charlotte
Zwick, Anabel
Mohr, Tobias
Gasparoni, Gilles
Khalmurzaev, Oybek
Matveev, Vsevolod Borisovich
Loertzer, Philine
Pryalukhin, Alexey
Hartmann, Arndt
Geppert, Carol-Immanuel
Loertzer, Hagen
Wunderlich, Heiko
Naumann, Carsten Maik
Kalthoff, Holger
Junker, Kerstin
Smola, Sigrun
Lohse, Stefan
Sprache: Englisch
Titel: Molecular Cancer Therapeutics
Bandnummer: 20
Heft: 2
Seiten: 423–437
Verlag/Plattform: American Association for Cancer Research
Erscheinungsjahr: 2021
DDC-Sachgruppe: 500 Naturwissenschaften
610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Squamous penile cancer displays a rare human papillomavirus (HPV)–associated tumor entity. Investigations on the molecular pathogenesis of HPV-driven penile cancer are impaired by the rareness of clinical specimens and, in particular, are missing relevant cell culture models. Here, we identified in HPV-positive penile cancer cell lines that HPV16 oncoproteins control TP63 expression by modulating critical regulators, while integration into the TP63 open reading frame facilitates oncogene expression. The resulting feed-forward loop leads to elevated p63 levels that in turn enhance the release of the neutrophil-recruiting chemokine CXCL8. Remarkably, elevated CXCL8 amounts lead to the increased surface exposition of the Fc receptor of human IgA antibodies, FcαRI, on neutrophils and correlated with a higher susceptibility to antibody-dependent neutrophil-mediated cytotoxicity (ADCC) using an EGFR-specific IgA2 antibody. IHC staining of tissue microarrays proved that elevated expression of p63 together with neutrophil infiltration were significantly more frequent in HPV-positive penile cancer displaying a higher tumor grade. In summary, we identified a promising marker profile of patients with penile cancer at higher risk for worse prognosis. However, these patients may benefit from immunotherapeutic approaches efficiently engaging neutrophils for tumor cell killing.
DOI der Erstveröffentlichung: 10.1158/1535-7163.MCT-20-0173
URL der Erstveröffentlichung: https://aacrjournals.org/mct/article/20/2/423/92969
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-377901
hdl:20.500.11880/34179
http://dx.doi.org/10.22028/D291-37790
ISSN: 1538-8514
1535-7163
Datum des Eintrags: 2-Nov-2022
Bezeichnung des in Beziehung stehenden Objekts: Supplementary data
In Beziehung stehendes Objekt: https://aacr.silverchair-cdn.com/aacr/content_public/journal/mct/20/2/10.1158_1535-7163.mct-20-0173/3/15357163mct200173-sup-238825_3_supp_6639207_q30y73.docx?Expires=1669975342&Signature=skBkpTc1FgniUW1AVlt2Jgg9YsgTFbu~S8VjgKPWJJ9oaHSLwY4CpeoaHrtuXHcPNRsHzT0fUFRZuTY12j5AZ~7fwdgcQilBJ~xeCOUM8uIWbr25YDUArGyzPHYbjTyY6j5AAlba99AAtCzkHKQckgfkJPK5iVMqhWAm~dZQAZItMMmfFKBfRX3jooNuuXaZ~T2U2ALv1cTKNOitOdbwgfW49wV8swaOB2GGJeaqnw5lGLp8aSewTJSkSMLvdMHxcH8wBuN5dyL-ENUM2nwg9OGHgwVYNQARniDKg6aeEr5qjX4tXl3KLoME2Uh8zYPYiGw5AtRyYcFWaLACLB4IdQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
https://aacr.silverchair-cdn.com/aacr/content_public/journal/mct/20/2/10.1158_1535-7163.mct-20-0173/3/15357163mct200173-sup-238825_3_supp_6639208_qr0y7r.docx?Expires=1669975342&Signature=IbKUBDlEJbqIHIXuoLyDvfyRQb2SuxOlrYFWe3YjmUKKDDOWUeyBvgbjObmE0mgLSg52sVvVb-wU~ngEcNyoedK2oHKspBI-8n2Rb0roRoTVNaE4Ydp9gb9l61FhZCk~26OLSjKoaxjaP5qNvit9PO8T3xW~n4DVeYPCIUaiDY1B~d~yjBVjPZz51~aA-4c7k-fMXVN6vAnj9BiaHuumnl~S59wxTOfNiB8l20tp1j7yAT9SyAyh22nDx-iaXQ2qnuvA-PlcvhHin30HVi5WtKyzUTZX-W2-JPsMBEDS1Cadgz~TKHXgNpw2tc4G3us2on-DgJV-czpSa69gFEp3Og__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
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Fakultät: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: M - Infektionsmedizin
M - Urologie und Kinderurologie
NT - Biowissenschaften
Professur: M - Prof. Dr. Sigrun Smola
M - Prof. Dr. Michael Stöckle
NT - Keiner Professur zugeordnet
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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