文章：

癌症中的中性粒细胞：不同肿瘤模型中的表型异质性及DNase I处理后淋巴肉瘤RLS40模型中脾中性粒细胞表型的显著改变

Neutrophils in Cancer: Phenotypic Heterogeneity Across Tumor Models and Significant Alteration of Splenic Neutrophil Phenotype in Lymphosarcoma RLS40Model Following DNase I Treatment

原文发布日期：12 August 2025

DOI: 10.3390/cancers17162631

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Neutrophils have recently gained significant attention due to their heterogeneity in tumor settings. Recent data showed neutrophil pro- and anti-tumor profiles during tumor progression. However, the concessive causes of neutrophil skewing toward one or another profile are not fully understood.Methods: In this study, using RT-qPCR, flowcytometry, and confocal microscopy, we investigated the phenotype of splenic neutrophils of mice bearing Lewis lung carcinoma LLC, RLS40lymphosarcoma, and B16 melanoma.Results: Our data showed an immunosuppressive phenotype in the case of the LLC model with PD-L1 and IL10 expression. In the B16 model, minimal changes in the neutrophil phenotype were observed, regardless of tumor size. In the RLS40model, the neutrophil phenotype was associated with the tumor growth rate, where, in aggressively progressed tumors (RLS40High), CCL17 was expressed, while, in mice with controlled tumor growth (RLS40Low), anti-tumor markers were expressed (FAS, ICAM-1, PD-L1). DNase I treatment significantly reduced tumor growth and metastasis in the RLS40model but not in B16, enhanced the anti-tumor profile in RLS40neutrophils, and tended to reduce NET formation induced by A23187.Conclusions: The phenotype of neutrophils from tumor-bearing mice is influenced by the tumor type and progression stage. DNase I had anti-tumor, antimetastatic, and immunostimulatory effects and significantly modified the neutrophil profile in the immunogenic model RLS40.

摘要翻译： 

背景/目的：中性粒细胞因其在肿瘤环境中的异质性而受到广泛关注。最新数据显示，中性粒细胞在肿瘤进展过程中表现出促肿瘤和抗肿瘤双重特性。然而，中性粒细胞向特定表型偏移的决定性因素尚未完全阐明。 方法：本研究通过实时荧光定量PCR、流式细胞术和共聚焦显微镜技术，系统分析了Lewis肺癌（LLC）、RLS40淋巴肉瘤和B16黑色素瘤荷瘤小鼠脾脏中性粒细胞的表型特征。 结果：数据显示，在LLC模型中，中性粒细胞呈现免疫抑制表型，表现为PD-L1和IL10的表达。B16模型中，无论肿瘤体积大小，中性粒细胞表型均未发生显著改变。在RLS40模型中，中性粒细胞表型与肿瘤生长速率相关：在快速进展的肿瘤（RLS40High）中检测到CCL17表达，而在肿瘤生长受控的小鼠（RLS40Low）中则表达抗肿瘤标志物（FAS、ICAM-1、PD-L1）。DNase I处理在RLS40模型中显著抑制肿瘤生长和转移（B16模型无此效应），增强中性粒细胞的抗肿瘤表型，并呈现抑制A23187诱导的NETs形成趋势。 结论：荷瘤小鼠中性粒细胞表型受肿瘤类型和进展阶段的双重影响。在免疫原性模型RLS40中，DNase I展现出抗肿瘤、抗转移及免疫刺激作用，并能显著重塑中性粒细胞的功能表型。

原文链接：

Neutrophils in Cancer: Phenotypic Heterogeneity Across Tumor Models and Significant Alteration of Splenic Neutrophil Phenotype in Lymphosarcoma RLS40Model Following DNase I Treatment