Xiao Yang, Niu Zijie, Ma Lijing, Wang Jun
Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang, Dongcheng District, Beijing 100730, China.
Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, No. 1 Dongjiaominxiang, Dongcheng District, Beijing 100730, China.
J Leukoc Biol. 2025 Jul 9;117(7). doi: 10.1093/jleuko/qiaf055.
Neutrophils are known to infiltrate various tumor tissues extensively and contribute to disease progression. However, the role of tumor-associated neutrophils in the pathogenesis of recurrent respiratory papillomatosis remains unclear. This study aimed to explore the prognostic significance of tumor-associated neutrophils and examine their role in the pathogenesis of recurrent respiratory papillomatosis. Immunohistochemistry was employed to assess the intensity of neutrophil infiltration in RRP tumor tissues. Multifactorial logistic regression analysis was conducted to evaluate the relationship between tumor-associated neutrophils and patient prognosis. Flow cytometry analysis was used to examine the phenotype of neutrophils. Additionally, coculture assays were performed with tumor-associated neutrophils and peripheral T cells to assess their functional interactions. Immunohistochemical analysis revealed that patients with recurrent respiratory papillomatosis exhibited significantly higher neutrophil densities within tumor tissues. Elevated neutrophil counts, neutrophil-to-lymphocyte ratio, and tumor-associated neutrophil infiltration were observed in patients with more aggressive forms of recurrent respiratory papillomatosis. Multivariate logistic regression identified the extent of neutrophil infiltration as an independent risk factor for an aggressive clinical course in these patients. Furthermore, tumor-associated neutrophils expressed high levels of CXCR1, CXCR2, and arginase 1, indicating a protumor phenotype, along with elevated levels of PD-L1, an immunosuppressive molecule. Functionally, these tumor-associated neutrophils effectively suppressed T-cell proliferation, activation, and cytokine secretion. Thus, tumor-associated neutrophils play a crucial role in fostering an immunosuppressive microenvironment that enables tumor immune evasion. This process initiates a positive feedback loop, where tumor cells secrete chemokines to recruit more neutrophils, thereby further accelerating tumor progression.
已知中性粒细胞会广泛浸润各种肿瘤组织并促进疾病进展。然而，肿瘤相关中性粒细胞在复发性呼吸道乳头状瘤病发病机制中的作用仍不清楚。本研究旨在探讨肿瘤相关中性粒细胞的预后意义，并研究它们在复发性呼吸道乳头状瘤病发病机制中的作用。采用免疫组织化学方法评估RRP肿瘤组织中中性粒细胞浸润的强度。进行多因素逻辑回归分析以评估肿瘤相关中性粒细胞与患者预后之间的关系。使用流式细胞术分析来检测中性粒细胞的表型。此外，进行肿瘤相关中性粒细胞与外周T细胞的共培养试验以评估它们的功能相互作用。免疫组织化学分析显示，复发性呼吸道乳头状瘤病患者的肿瘤组织中中性粒细胞密度显著更高。在侵袭性更强的复发性呼吸道乳头状瘤病患者中观察到中性粒细胞计数、中性粒细胞与淋巴细胞比值以及肿瘤相关中性粒细胞浸润升高。多变量逻辑回归确定中性粒细胞浸润程度是这些患者侵袭性临床病程的独立危险因素。此外，肿瘤相关中性粒细胞表达高水平的CXCR1、CXCR2和精氨酸酶1，表明具有促肿瘤表型，同时免疫抑制分子PD-L1水平升高。在功能上，这些肿瘤相关中性粒细胞有效抑制T细胞增殖、激活和细胞因子分泌。因此，肿瘤相关中性粒细胞在促进免疫抑制微环境以实现肿瘤免疫逃逸方面起着关键作用。这一过程启动了一个正反馈循环，肿瘤细胞分泌趋化因子以招募更多中性粒细胞，从而进一步加速肿瘤进展。
