Eckel Hans N C, Lyu Su Ir, Faste Frederik, Sharma Shachi J, Nobis Anne, Wuerdemann Nora, Ziogas Maria, Mayer Marcel, Suchan Malte C, Wennhold Kerstin, Garcia-Marquez Maria A, Thelen Martin, Hagen Elena, Eßer Julia, Klasen Charlotte, Siefer Oliver, Otte Martin, Schloesser Hans A, Klussmann Jens P, Quaas Alexander, Hansen Kevin K
Faculty of Medicine and University Hospital of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, 50931 Cologne, Germany.
Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50931 Cologne, Germany.
Cells. 2025 Jun 27;14(13):985. doi: 10.3390/cells14130985.
Human papillomavirus-mediated recurrent respiratory papillomatosis (RRP) is a premalignant neoplasia of the upper airway characterized by significant dysphonia and respiratory obstruction. Immune checkpoint blockade has emerged as a potential alternative to repeated surgical interventions in RRP. Here, we investigated the intralesional T-cell composition and expression of the immune checkpoints programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) in RRP. We analyzed tissue samples from 30 patients treated at a tertiary care center between 2009 and 2021, including paired samples from individual patients collected at different time points. Immunohistochemical staining was performed for CD4, CD8, CTLA-4, FoxP3, and PD-L1 and correlated with disease severity and previous adjuvant therapies. Overall disease burden and intervention-free survival were not associated with the abundance of CD4, CD8, or FoxP3 T cells, nor with immune checkpoint expression. However, patients with aggressive disease exhibited a higher intralesional FoxP3/CD4 T-cell ratio. Prior intralesional cidofovir treatment was associated with reduced CD4 T-cell infiltration. These findings suggest that a locally immunosuppressive microenvironment, reflected by an elevated FoxP3/CD4 ratio, contributes to disease severity in RRP. Consistent CTLA-4 expression across all evaluated samples supports further investigation of anti-CTLA-4 therapy, either alone or in combination with other checkpoint inhibitors.
人乳头瘤病毒介导的复发性呼吸道乳头状瘤病(RRP)是一种上呼吸道的癌前肿瘤,其特征为严重的发音障碍和呼吸阻塞。免疫检查点阻断已成为RRP中重复手术干预的一种潜在替代方法。在此,我们研究了RRP中瘤内T细胞组成以及免疫检查点程序性死亡配体1(PD-L1)和细胞毒性T淋巴细胞抗原4(CTLA-4)的表达。我们分析了2009年至2021年间在一家三级医疗中心接受治疗的30例患者的组织样本,包括来自个体患者在不同时间点采集的配对样本。对CD4、CD8、CTLA-4、FoxP3和PD-L1进行免疫组织化学染色,并与疾病严重程度和先前的辅助治疗相关联。总体疾病负担和无干预生存期与CD4、CD8或FoxP3 T细胞的丰度以及免疫检查点表达均无关。然而,侵袭性疾病患者的瘤内FoxP3/CD4 T细胞比值较高。先前瘤内注射西多福韦治疗与CD4 T细胞浸润减少有关。这些发现表明,FoxP3/CD4比值升高所反映的局部免疫抑制微环境促成了RRP的疾病严重程度。所有评估样本中CTLA-4表达一致,这支持进一步研究抗CTLA-4疗法,单独使用或与其他检查点抑制剂联合使用。