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Peer-reviewedCC BYViruses

HPV6/11 Persistence and Treatment-Associated Immune Remodeling in Recurrent Respiratory Papillomatosis: A Cross-Cohort Transcriptomic Analysis.

4 affiliations
  1. 1Research and Development Center, Regional Specialist Hospital in Wroclaw, 51-124 Wroclaw, Poland.
  2. 2Laboratory of Phage Molecular Biology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland.
  3. 3Faculty of Medicine, Wroclaw University of Science and Technology, 50-370 Wroclaw, Poland.
  4. 4Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.

Abstract

Recurrent respiratory papillomatosis (RRP), caused mainly by human papillomavirus types 6 and 11 (HPV6/11), can persist despite the absence of recognized systemic immunodeficiency. We reanalyzed three transcriptomic datasets using the same predefined immune-gene programs: paired papilloma and autologous laryngeal mucosa from 12 patients, single-cell RNA sequencing from papillomas of four RRP donors and pharyngopalatine mucosa from three controls, and paired papilloma samples from 17 patients before and after INO-3107, a DNA immunotherapy encoding HPV6/11 antigens and interleukin-12. In untreated tissue, cluster of differentiation 8 (CD8)- and natural killer (NK)-associated cytotoxic program scores were lower and the transforming growth factor beta (TGF-β) suppressive program score was higher, reproducing findings from the same cohort. The lower cytotoxic pattern was not reproduced within the recovered combined T-cell and NK-cell population, although no single-cell comparison remained significant after correction for multiple testing. After INO-3107, CD8- and NK-associated cytotoxic, T helper 1 (Th1)/interferon gamma (IFN-γ), and C-X-C motif chemokine receptor 3 (CXCR3)-associated trafficking program scores increased significantly, whereas TGF-β and M2-like suppressive programs showed no comparable statistically supported change. Together, these findings show that different components of the local immune response do not change in parallel and support a model of selective treatment-associated immune remodeling. This pattern may inform future biomarker and combination-treatment studies.

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BibTeX
@article{jedruchniewicz2026hpv611,
  title = {{HPV6/11 Persistence and Treatment-Associated Immune Remodeling in Recurrent Respiratory Papillomatosis: A Cross-Cohort Transcriptomic Analysis.}},
  author = {Natalia Jędruchniewicz and Tomasz Klimek and Hanna Klimza and Krystyna Dąbrowska and Małgorzata Wierzbicka},
  journal = {Viruses},
  year = {2026},
  month = sep,
  doi = {10.3390/v18101080},
  url = {https://europepmc.org/article/MED/42944000},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - HPV6/11 Persistence and Treatment-Associated Immune Remodeling in Recurrent Respiratory Papillomatosis: A Cross-Cohort Transcriptomic Analysis.
AU  - Natalia Jędruchniewicz
AU  - Tomasz Klimek
AU  - Hanna Klimza
AU  - Krystyna Dąbrowska
AU  - Małgorzata Wierzbicka
PY  - 2026
DA  - 2026/09/30
JO  - Viruses
DO  - 10.3390/v18101080
UR  - https://europepmc.org/article/MED/42944000
AB  - Recurrent respiratory papillomatosis (RRP), caused mainly by human papillomavirus types 6 and 11 (HPV6/11), can persist despite the absence of recognized systemic immunodeficiency. We reanalyzed three transcriptomic datasets using the same predefined immune-gene programs: paired papilloma and autologous laryngeal mucosa from 12 patients, single-cell RNA sequencing from papillomas of four RRP donors and pharyngopalatine mucosa from three controls, and paired papilloma samples from 17 patients before and after INO-3107, a DNA immunotherapy encoding HPV6/11 antigens and interleukin-12. In untreated tissue, cluster of differentiation 8 (CD8)- and natural killer (NK)-associated cytotoxic program scores were lower and the transforming growth factor beta (TGF-β) suppressive program score was higher, reproducing findings from the same cohort. The lower cytotoxic pattern was not reproduced within the recovered combined T-cell and NK-cell population, although no single-cell comparison remained significant after correction for multiple testing. After INO-3107, CD8- and NK-associated cytotoxic, T helper 1 (Th1)/interferon gamma (IFN-γ), and C-X-C motif chemokine receptor 3 (CXCR3)-associated trafficking program scores increased significantly, whereas TGF-β and M2-like suppressive programs showed no comparable statistically supported change. Together, these findings show that different components of the local immune response do not change in parallel and support a model of selective treatment-associated immune remodeling. This pattern may inform future biomarker and combination-treatment studies.
SN  - 1999-4915
ER  -