The HPV and p63 status in penile cancer are linked with the infiltration and therapeutic availability of neutrophils

Bernhard MC, Zwick A, Mohr T, Gasparoni G, Khalmurzaev O, Matveev VB, Loertzer P, Pryalukhin A, Hartmann A, Geppert CI, Loertzer H, Wunderlich H, Naumann CM, Kalthoff H, Junker K, Smola S, Lohse S (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Molecular Cancer Therapeutics American Association for Cancer Research

Book Volume: 20

Pages Range: 423-437

Journal Issue: 2

DOI: 10.1158/1535-7163.MCT-20-0173

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, FcaRI, 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.

Authors with CRIS profile

Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Carol-Immanuel Geppert Institute of Pathology

Involved external institutions

Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Westpfalz-Klinikum DE Germany (DE) Ministry of Health of the Russian Federation / Министерство здравоохранения Российской Федерации RU Russian Federation (RU) Universität des Saarlandes (UdS) DE Germany (DE)

How to cite

APA:

Bernhard, M.C., Zwick, A., Mohr, T., Gasparoni, G., Khalmurzaev, O., Matveev, V.B.,... Lohse, S. (2021). The HPV and p63 status in penile cancer are linked with the infiltration and therapeutic availability of neutrophils. Molecular Cancer Therapeutics, 20(2), 423-437. https://doi.org/10.1158/1535-7163.MCT-20-0173

MLA:

Bernhard, Muriel Charlotte, et al. "The HPV and p63 status in penile cancer are linked with the infiltration and therapeutic availability of neutrophils." Molecular Cancer Therapeutics 20.2 (2021): 423-437.

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