Laryngeal papilloma (LP) is a rare benign disease, caused by recurrent multisite papillomas that are referred to as recurrent respiratory papillomatosis (RRP). RRP is caused primarily by two types of human papillomavirus (HPV): HPV6 and HPV11. The immune dysregulation within the microenvironment of the lesions has been shown to likely play a role in the development of RRP. The present study aimed at analyzing the transcriptional profile of immune response genes and cancer-related genes in the LP microenvironment. We used the NanoString® nCounter® analysis system to study expression of 730 genes among seven paired samples of LP and healthy laryngeal (HL) tissue. qRT-PCR and flow cytometric analysis was performed to confirm identified transcripts and follow-up scores of infiltrating immune cells, respectively. In total, 113 differentially expressed transcripts were detected of which 37 showed increased expression levels and 76 decreased expression levels in the LP samples compared to the HL samples (fold change ≥ 2). Transcripts with increased expression levels included S100As (A7, A8, and A12), CEACAM1, neutrophil activation associated cytokines (IL8), chemokines (CXCL6), and IL receptors, e.g., IL4R. Transcripts with decreased expression in LP were associated with innate and adaptive immunity. Overall, HPV6 and 11 were present in 67% and 33% of the patients, respectively. There was a significant increase in neutrophils and a significant decrease in CD8+ T cells in LP. LP samples display an immune profile characterized by enhanced expression of neutrophilic markers and significantly reduced T cell-associated markers.
Bibliografisk informationFunding Information:
We thank Susanna Tarasco, Andy Forreryd and Tim Lindberg for technical assistance, and Dr. Malin Josefsson and Dr. Henrik Widegren for the samples collection. This work was financially supported by grants from the Marie Skłodowska‐Curie program CanFaster‐ Translational cancer faster forward doctoral program (744299), the Faculty of Engineering, Lund University, Lions Research Foundation Skåne (Grant ID 81204), Laryngfonden (Grant ID 40‐16), Lions Research Foundation Norrland (Grant ID 1818–925), AMP (Grant ID 19–973), Västerbotten county council C‐ALF (Grant ID 7003128) and PR2017‐0163 Swedish Childhood Cancer Fund. Graphical abstract created with BioRender.com.
© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH
Copyright 2021 Elsevier B.V., All rights reserved.
- Immunologi inom det medicinska området