Department of Immunotechnology, Lund University, Lund, Sweden.
Department of Medical Microbiology, Lund University, Lund, Sweden.
Eur J Immunol. 2021 Oct;51(10):2535-2539. doi: 10.1002/eji.202149202. Epub 2021 Aug 16.
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.
喉乳头状瘤(LP)是一种罕见的良性疾病,由复发性多部位的乳头状瘤引起,这种疾病被称为复发性呼吸道乳头状瘤病(RRP)。RRP 主要由两种人类乳头瘤病毒(HPV)引起:HPV6 和 HPV11。病变微环境中的免疫失调可能在 RRP 的发展中起作用。本研究旨在分析 LP 微环境中免疫反应基因和癌症相关基因的转录谱。我们使用 NanoString nCounter 分析系统研究了 7 对 LP 和健康喉(HL)组织样本中的 730 个基因的表达情况。qRT-PCR 和流式细胞术分析分别用于确认鉴定的转录本和浸润免疫细胞的后续评分。总共检测到 113 个差异表达的转录本,其中 37 个在 LP 样本中表达水平升高,76 个在 LP 样本中表达水平降低与 HL 样本相比(倍数变化≥2)。表达水平升高的转录本包括 S100As(A7、A8 和 A12)、CEACAM1、中性粒细胞激活相关细胞因子(IL8)、趋化因子(CXCL6)和 IL 受体,例如 IL4R。在 LP 中表达降低的转录本与先天和适应性免疫有关。总体而言,HPV6 和 11 分别存在于 67%和 33%的患者中。LP 中中性粒细胞显著增加,CD8 T 细胞显著减少。LP 样本显示出免疫特征,其特征为中性粒细胞标志物表达增强,与 T 细胞相关的标志物显著减少。