PDF(Pubmed)
Abstract：
OBJECTIVE: To characterize the distribution of immune cell subsets within laryngeal papillomas and to study the function of potentially immunosuppressive neutrophilic and regulatory T cells (Tregs).
METHODS: Fresh clinical papilloma specimens were collected at the time of surgery and studied with multiparameter flow cytometry. Papilloma infiltrating neutrophilic cells and Tregs were sorted and studied functionally with ex vivo T cell suppression assays.
RESULTS: Flow cytometric analysis of fresh laryngeal papillomas samples from 18 adult patients with recurrent respiratory papillomatosis revealed patterns in immune constituency between patients. Clearly divergent phenotypes based primarily on the degree of neutrophilic and T cell infiltration were identified. Relative neutrophilic cell enrichment and T cell depletion were observed in 50% of samples and neutrophilic cell depletion and T cell enrichment were observed in the others. Greater papilloma neutrophilic cell enrichment was positively associated with the number of clinically indicated interventions required in the 12 months prior to sample collection, linking papilloma neutrophil inflammation to disease severity. Functional assays revealed the ability of both papilloma infiltrating neutrophilic and Tregs to suppress T cell function at roughly equal magnitudes, but substantially increased infiltration of neutrophilic cells compared to Tregs across samples.
CONCLUSIONS: Neutrophilic cells are an important contributor to immunosuppression within the respiratory papilloma microenvironment. Given these data and the association between greater neutrophilic cell infiltration and lack of clinical response to therapeutic vaccination, additional study of strategies aimed at limiting neutrophilic cell infiltration or function within papillomas is warranted.
METHODS: 4 Laryngoscope, 134:3238-3244, 2024.
METHODS: Fresh clinical papilloma specimens were collected at the time of surgery and studied with multiparameter flow cytometry. Papilloma infiltrating neutrophilic cells and Tregs were sorted and studied functionally with ex vivo T cell suppression assays.
RESULTS: Flow cytometric analysis of fresh laryngeal papillomas samples from 18 adult patients with recurrent respiratory papillomatosis revealed patterns in immune constituency between patients. Clearly divergent phenotypes based primarily on the degree of neutrophilic and T cell infiltration were identified. Relative neutrophilic cell enrichment and T cell depletion were observed in 50% of samples and neutrophilic cell depletion and T cell enrichment were observed in the others. Greater papilloma neutrophilic cell enrichment was positively associated with the number of clinically indicated interventions required in the 12 months prior to sample collection, linking papilloma neutrophil inflammation to disease severity. Functional assays revealed the ability of both papilloma infiltrating neutrophilic and Tregs to suppress T cell function at roughly equal magnitudes, but substantially increased infiltration of neutrophilic cells compared to Tregs across samples.
CONCLUSIONS: Neutrophilic cells are an important contributor to immunosuppression within the respiratory papilloma microenvironment. Given these data and the association between greater neutrophilic cell infiltration and lack of clinical response to therapeutic vaccination, additional study of strategies aimed at limiting neutrophilic cell infiltration or function within papillomas is warranted.
METHODS: 4 Laryngoscope, 134:3238-3244, 2024.
摘要：
目的：研究喉乳头状瘤中免疫细胞亚群的分布，并研究潜在免疫抑制性中性粒细胞和调节性T细胞（Tregs）的功能。
方法：在手术时收集新鲜的临床乳头状瘤标本，并用多参数流式细胞术进行研究。对乳头状瘤浸润性嗜中性粒细胞和Treg进行分选，并用离体T细胞抑制测定法进行功能研究。
结果：对18例复发性呼吸道乳头状瘤成年患者的新鲜喉乳头状瘤样本进行的流式细胞术分析显示患者之间的免疫调节模式。鉴定了主要基于嗜中性粒细胞和T细胞浸润程度的明显不同的表型。在50％的样品中观察到相对的嗜中性粒细胞富集和T细胞耗竭，在其他样品中观察到嗜中性粒细胞耗竭和T细胞富集。更多的乳头状瘤嗜中性粒细胞富集与样本收集前12个月内所需的临床指示干预措施的数量呈正相关。将乳头状瘤中性粒细胞炎症与疾病严重程度联系起来。功能测定显示乳头状瘤浸润嗜中性粒细胞和Tregs抑制T细胞功能的能力大致相等，但与样本中的Tregs相比，嗜中性细胞的浸润大大增加。
结论：嗜中性粒细胞是呼吸道乳头状瘤微环境中免疫抑制的重要因素。鉴于这些数据以及更多嗜中性粒细胞浸润与缺乏治疗性疫苗接种的临床反应之间的关联，有必要进一步研究旨在限制嗜中性粒细胞浸润或乳头状瘤功能的策略.
方法：4喉镜，2024.
方法：在手术时收集新鲜的临床乳头状瘤标本，并用多参数流式细胞术进行研究。对乳头状瘤浸润性嗜中性粒细胞和Treg进行分选，并用离体T细胞抑制测定法进行功能研究。
结果：对18例复发性呼吸道乳头状瘤成年患者的新鲜喉乳头状瘤样本进行的流式细胞术分析显示患者之间的免疫调节模式。鉴定了主要基于嗜中性粒细胞和T细胞浸润程度的明显不同的表型。在50％的样品中观察到相对的嗜中性粒细胞富集和T细胞耗竭，在其他样品中观察到嗜中性粒细胞耗竭和T细胞富集。更多的乳头状瘤嗜中性粒细胞富集与样本收集前12个月内所需的临床指示干预措施的数量呈正相关。将乳头状瘤中性粒细胞炎症与疾病严重程度联系起来。功能测定显示乳头状瘤浸润嗜中性粒细胞和Tregs抑制T细胞功能的能力大致相等，但与样本中的Tregs相比，嗜中性细胞的浸润大大增加。
结论：嗜中性粒细胞是呼吸道乳头状瘤微环境中免疫抑制的重要因素。鉴于这些数据以及更多嗜中性粒细胞浸润与缺乏治疗性疫苗接种的临床反应之间的关联，有必要进一步研究旨在限制嗜中性粒细胞浸润或乳头状瘤功能的策略.
方法：4喉镜，2024.
