Robbins Yvette, Lassoued Wiem, Bai Ke, Huynh Angel, Norberg Scott M, Allen Clint T
Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Laryngoscope. 2025 Aug;135(8):2824-2830. doi: 10.1002/lary.32121. Epub 2025 Mar 13.
Prior studies have reported low or absent major HLA class I expression on respiratory papilloma cells, conflicting with the recent clinical success of immunotherapy designed to activate HPV-specific T cells in patients with recurrent respiratory papillomatosis (RRP). We aimed to determine major human leukocyte antigen (HLA) class I expression on respiratory papilloma cells in untreated RRP clinical specimens using contemporary techniques.
Formalin-fixed, paraffin-embedded RRP sections were subjected to signal-amplified multispectral immunofluorescence using the OPAL system to determine major and minor HLA class I expression, and digitally scanned slides were analyzed using digital pathology software. Positive and negative controls were used to optimize primary antibody conditions.
All samples harbored major HLA class I expression on varying proportions of papilloma cells. Considering all samples, major HLA class I expression was observed on the majority (74%) of papilloma cells. Nearly all (98%) papilloma infiltrating immune cells were positive for major HLA class I expression, serving as an internal control for each stained sample. Major HLA class I negative papilloma cells were enriched in the apical, suprabasal layers compared to the basal layers of the papillomatous epithelium, suggesting an association with the epithelial cell differentiation state. Fewer papilloma cells inconsistently expressed the minor HLA class I HLA-E across the basal and suprabasal epithelial layers.
Papilloma cells express major HLA class I molecules. Using contemporary immunofluorescent techniques with signal amplification that likely provide improved sensitivity, these results clarify the major HLA class I expression status on papilloma cells in clinical specimens.
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先前的研究报告称，呼吸道乳头瘤细胞上主要组织相容性复合体I类分子（MHC I类分子）表达水平较低或无表达，这与近期旨在激活复发性呼吸道乳头瘤病（RRP）患者中HPV特异性T细胞的免疫疗法所取得的临床成功相矛盾。我们旨在使用现代技术确定未经治疗的RRP临床标本中呼吸道乳头瘤细胞上主要人类白细胞抗原（HLA）I类分子的表达情况。
使用OPAL系统对福尔马林固定、石蜡包埋的RRP切片进行信号放大多光谱免疫荧光检测，以确定主要和次要HLA I类分子的表达情况，并使用数字病理软件对数字扫描的玻片进行分析。使用阳性和阴性对照来优化一抗条件。
所有样本中不同比例的乳头瘤细胞均表达主要HLA I类分子。综合所有样本来看，大多数（74%）乳头瘤细胞表达主要HLA I类分子。几乎所有（98%）浸润乳头瘤的免疫细胞均表达主要HLA I类分子阳性，可作为每个染色样本的内部对照。与乳头瘤上皮的基底层相比，主要HLA I类分子阴性的乳头瘤细胞在表层和基底上层更为富集，提示其与上皮细胞分化状态有关。在基底和基底上层上皮中，较少的乳头瘤细胞不一致地表达次要HLA I类分子HLA-E。
乳头瘤细胞表达主要HLA I类分子。使用可能具有更高灵敏度的现代信号放大免疫荧光技术所得到的这些结果，阐明了临床标本中乳头瘤细胞上主要HLA I类分子的表达状况。
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