Local T-Cell Dysregulation and Immune Checkpoint Expression in Human Papillomavirus-Mediated Recurrent Respiratory Papillomatosis

Local T-Cell Dysregulation and Immune Checkpoint Expression in Human Papillomavirus-Mediated Recurrent Respiratory Papillomatosis

Human papillomavirus-mediated recurrent respiratory papillomatosis (RRP) is a premalignant neoplasia of the upper airway characterized by significant dysphonia and respiratory obstruction. Immune checkpoint blockade has emerged as a potential alternative to repeated surgical interventions in RRP. He...

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Main Authors: Hans N. C. Eckel, Su Ir Lyu, Frederik Faste, Shachi J. Sharma, Anne Nobis, Nora Wuerdemann, Maria Ziogas, Marcel Mayer, Malte C. Suchan, Kerstin Wennhold, Maria A. Garcia-Marquez, Martin Thelen, Elena Hagen, Julia Eßer, Charlotte Klasen, Oliver Siefer, Martin Otte, Hans A. Schloesser, Jens P. Klussmann, Alexander Quaas, Kevin K. Hansen
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Cells
Subjects:
human papillomavirus
recurrent respiratory papillomatosis
lymphocytes
CTLA4
Online Access:https://www.mdpi.com/2073-4409/14/13/985
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Summary:Human papillomavirus-mediated recurrent respiratory papillomatosis (RRP) is a premalignant neoplasia of the upper airway characterized by significant dysphonia and respiratory obstruction. Immune checkpoint blockade has emerged as a potential alternative to repeated surgical interventions in RRP. Here, we investigated the intralesional T-cell composition and expression of the immune checkpoints programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) in RRP. We analyzed tissue samples from 30 patients treated at a tertiary care center between 2009 and 2021, including paired samples from individual patients collected at different time points. Immunohistochemical staining was performed for CD4, CD8, CTLA-4, FoxP3, and PD-L1 and correlated with disease severity and previous adjuvant therapies. Overall disease burden and intervention-free survival were not associated with the abundance of CD4<sup>+</sup>, CD8<sup>+</sup>, or FoxP3<sup>+</sup> T cells, nor with immune checkpoint expression. However, patients with aggressive disease exhibited a higher intralesional FoxP3/CD4 T-cell ratio. Prior intralesional cidofovir treatment was associated with reduced CD4<sup>+</sup> T-cell infiltration. These findings suggest that a locally immunosuppressive microenvironment, reflected by an elevated FoxP3/CD4 ratio, contributes to disease severity in RRP. Consistent CTLA-4 expression across all evaluated samples supports further investigation of anti-CTLA-4 therapy, either alone or in combination with other checkpoint inhibitors.
ISSN:2073-4409

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