The CXCLs-CXCR2 axis modulates the cross-communication between tumor-associated neutrophils and tumor cells in cervical cancer.

IF 3.9 3区医学 Q2 IMMUNOLOGY Expert Review of Clinical Immunology Pub Date : 2024-05-01 Epub Date: 2024-01-24 DOI:10.1080/1744666X.2024.2305808

Hai-Zhou Ji, Bin Liu, Mi Ren, Sang Li, Jian-Feng Zheng, Tong-Yu Liu, Hui-Hui Yu, Yang Sun

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Abstract

Objective: This study aimed to check the expression profile of the C-X-C motif chemokine ligands (CXCLs)-C-X-C motif chemokine receptor 2 (CXCR2) axis in cervical cancer and to explore the cross-talk between cervical cancer cells and neutrophils via CXCLs-CXCR2 axis.

Methods: Available RNA-sequencing data based on bulk tissues and single-cell/nucleus RNA-sequencing data were used for bioinformatic analysis. Cervical cancer cell lines Hela and SiHa cells were utilized for in vitro and in vivo studies.

Results: Except for neutrophils, CXCR2 mRNA expression is limited in other types of cells in the cervical tumor microenvironment. CXCLs bind to CXCR2 and are mainly expressed by tumor cells. CXCL1, 2, 3, 5, 6, and 8, which are consistently associated with neutrophil infiltration, are also linked to poor prognosis. SB225002 (a CXCR2 inhibitor) treatment significantly impairs SiHa cell-induced neutrophil migration. CXCL1, CXCL2, CXCL5, or CXCL8 neutralized conditioned medium from SiHa cells have weaker recruiting effects. The conditioned medium of neutrophils from healthy donors can slow cancer cell proliferation. Conditioned medium of tumor-associated neutrophils (TANs) can drastically enhance cervical cancer cell growth in vitro and in vivo.

Conclusions: The CXCLs-CXCR2 axis is critical in neutrophil recruitment and tumor cell proliferation in the cervical cancer microenvironment.

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CXCLs-CXCR2 轴调节宫颈癌中肿瘤相关中性粒细胞与肿瘤细胞之间的交叉通讯。

研究目的本研究旨在检测 C-X-C motif 趋化因子配体（CXCLs）-C-X-C motif 趋化因子受体 2（CXCR2）轴在宫颈癌中的表达谱，并探讨宫颈癌细胞与中性粒细胞之间通过 CXCLs-CXCR2 轴的交叉对话：方法：利用现有的基于大块组织的 RNA 序列数据和单细胞/细胞核 RNA 序列数据进行生物信息学分析。宫颈癌细胞系 Hela 和 SiHa 细胞被用于体外和体内研究：结果：除中性粒细胞外，CXCR2 mRNA在宫颈肿瘤微环境中的其他类型细胞中的表达有限。CXCL 与 CXCR2 结合，主要由肿瘤细胞表达。CXCL1、2、3、5、6 和 8 始终与中性粒细胞浸润相关，也与预后不良有关。SB225002（一种 CXCR2 抑制剂）能显著抑制 SiHa 细胞诱导的中性粒细胞迁移。CXCL1、CXCL2、CXCL5或CXCL8中和的SiHa细胞条件培养基的招募作用较弱。健康供体中性粒细胞的条件培养基可减缓癌细胞增殖。肿瘤相关中性粒细胞（TANs）的条件培养基可显著促进宫颈癌细胞在体外和体内的生长：结论：CXCLs-CXCR2 轴在中性粒细胞招募和宫颈癌微环境中的肿瘤细胞增殖中至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Clinical Immunology IMMUNOLOGY-

CiteScore

7.60

自引率

2.30%

发文量

221

审稿时长

6-12 weeks

期刊介绍： Expert Review of Clinical Immunology (ISSN 1744-666X) provides expert analysis and commentary regarding the performance of new therapeutic and diagnostic modalities in clinical immunology. Members of the International Editorial Advisory Panel of Expert Review of Clinical Immunology are the forefront of their area of expertise. This panel works with our dedicated editorial team to identify the most important and topical review themes and the corresponding expert(s) most appropriate to provide commentary and analysis. All articles are subject to rigorous peer-review, and the finished reviews provide an essential contribution to decision-making in clinical immunology. Articles focus on the following key areas: • Therapeutic overviews of specific immunologic disorders highlighting optimal therapy and prospects for new medicines • Performance and benefits of newly approved therapeutic agents • New diagnostic approaches • Screening and patient stratification • Pharmacoeconomic studies • New therapeutic indications for existing therapies • Adverse effects, occurrence and reduction • Prospects for medicines in late-stage trials approaching regulatory approval • Novel treatment strategies • Epidemiological studies • Commentary and comparison of treatment guidelines Topics include infection and immunity, inflammation, host defense mechanisms, congenital and acquired immunodeficiencies, anaphylaxis and allergy, systemic immune diseases, organ-specific inflammatory diseases, transplantation immunology, endocrinology and diabetes, cancer immunology, neuroimmunology and hematological diseases.