Profiling of VEGF Receptors and Immune Checkpoints in Recurrent Respiratory Papillomatosis.
Profiling of VEGF Receptors and Immune Checkpoints in Recurrent Respiratory Papillomatosis.
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复发性呼吸道乳头状瘤病中 VEGF 受体和免疫检查点的分析。
DOI：
10.1002/lary.31253
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Best,SimonR
中科院分区：
文献类型：
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作者：
Lam,Brandon;Miller,Jonas;Kung,YuJui;Wu,TC;Hung,Chien-Fu;Roden,RichardBS;Best,SimonR
目的复发性呼吸道乳头状瘤病（RRP）是由人乳头状瘤病毒（HPV）感染空气消化道引起的，严重影响生活质量，包括沟通和呼吸的能力。传统上，治疗仅限于手术室的一系列消融手术和可能的局部辅助治疗，但新的全身治疗，如血管内皮生长因子（VEGF）抑制剂，显示出显著的前景。本研究旨在确定是否存在使用VEGF抑制剂和/或免疫检查点阻断联合治疗的理由。方法使用手术室新鲜标本，对乳头状瘤、正常邻近组织和血液进行流式细胞术检测。检测乳头瘤和周围组织PD‐L1、PD‐L2、Galectin‐9、VEGFR2和VEGFR3的表达。检测CD8+和CD4+ T细胞PD‐1、TIGIT、LAG3和TIM3的表达。结果我们的数据显示，与邻近组织相比，乳头状瘤组织中PD‐L1和PD‐L2的水平明显更高。在乳头状瘤组织中也观察到VEGF受体VEGFR3水平升高。当检查乳头状瘤内的T细胞时，CD8+ T细胞中PD‐1和TIGIT的表达升高，而CD4+ T细胞中PD‐1、TIGIT和TIM3的表达水平与PBMCs相比升高。个体间存在异质标记表达。结论sour分析显示，RRP组织中多个免疫检查点靶点和VEGFR3水平升高，且每个乳头瘤患者具有不同的模式。其中一些免疫检查点标记已经有新的免疫疗法可用或正在开发中，为RRP和VEGF抑制剂共同影响的患者提供这些全身治疗提供了分子基础。喉镜杂志，34 (4):519 - 525,2024
ObjectivesRecurrent respiratory papillomatosis (RRP) is caused by human papilloma virus (HPV) infection of the aerodigestive tract that significantly impacts quality‐of‐life including the ability to communicate and breathe. Treatment was traditionally limited to serial ablative procedures in the O.R. with possible local adjuvant therapy, but new systemic therapies, such as Vascular endothelial growth factor (VEGF) inhibitors, are showing significant promise. This study aims to determine whether rationale exists for combination therapeutic approaches using VEGF inhibitors and/or immune checkpoint blockade.MethodsUsing fresh specimens from the O.R., we performed flow cytometry on papilloma, normal adjacent tissue, and blood. Papilloma and surrounding tissue were examined for expression of PD‐L1, PD‐L2, Galectin‐9, VEGFR2, and VEGFR3. CD8+ and CD4+ T cells were assayed for expression of PD‐1, TIGIT, LAG3, and TIM3.ResultsOur data shows that papilloma tissue exhibits significantly higher levels of PD‐L1 and PD‐L2 compared to adjacent tissue. Elevated levels of the VEGF receptor VEGFR3 were also observed in papilloma tissue. When examining T cells within the papilloma, elevated PD‐1 and TIGIT expression was observed on CD8+ T cells, while levels of PD‐1, TIGIT, and TIM3 were elevated on CD4+ T cells compared to PBMCs. Heterogenous marker expression was observed between individuals.ConclusionsOur analysis shows that RRP tissue shows elevated levels of multiple immune check point targets and VEGFR3, with varied patterns unique to each papilloma patient. Some of these immune checkpoint markers already have novel immunotherapies available or in development, providing molecular rationale to offer these systemic treatments to selected patients affected by RRP alongside VEGF inhibitors.Laryngoscope, 134:2819–2825, 2024