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CXCL10在癌症进展中的双重作用:对免疫治疗和靶向治疗的启示

Dual role of CXCL10 in cancer progression: implications for immunotherapy and targeted treatment‎.

作者信息

Madkhali Osama A, Moni Sivakumar S, Almoshari Yosif, Sabei Fahad Y, Safhi Awaji Y

机构信息

Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan, Saudi ‎‎‎Arabia.

Health Research Centre, Jazan University, Jazan, Saudi Arabia.

出版信息

Cancer Biol Ther. 2025 Dec;26(1):2538962. doi: 10.1080/15384047.2025.2538962. Epub 2025 Aug 4.

Abstract

CXCL10 is a chemokine crucial for immune cell recruitment and inflammation modulation, especially ‎within the tumor microenvironment.‎ This review critically analyzes the underexplored role of CXCL10 in modulating ‎JAK/STAT, MAPK/ERK, and PI3K/Akt pathways across different tumor types, highlighting ‎inconsistencies in current research and proposing novel therapeutic strategies based on ‎research ‎from databases such as PubMed and Scopus. Future targeted therapies could ‎include personalized ‎approaches that either enhance the immunostimulatory functions of CXCL10‎ or inhibit its tumor promoting effects. Techniques such as CRISPR/Cas9-mediated knockout of CXCL10 has demonstrated potential in preclinical models to ‎reduce tumor-promoting inflammation, while nanoparticle-based CXCL10 inhibitors enhance ‎immune checkpoint blockade efficacy in melanoma. In addition, targeting CXCL10-related mechanisms of immune evasion such as inhibition of CXCR3 may help to prevent metastasis. Futureresearch should focus on CXCL10-targeting approaches in highly immunosuppressive tumors, such as pancreatic and glioblastoma, where immune checkpoint inhibitors have shown limited efficacy.

摘要

CXCL10是一种趋化因子,对免疫细胞募集和炎症调节至关重要,尤其是在肿瘤微环境中。本综述批判性地分析了CXCL10在调节不同肿瘤类型中的JAK/STAT、MAPK/ERK和PI3K/Akt信号通路方面未被充分探索的作用,强调了当前研究中的不一致之处,并基于来自PubMed和Scopus等数据库的研究提出了新的治疗策略。未来的靶向治疗可能包括个性化方法,即增强CXCL10的免疫刺激功能或抑制其肿瘤促进作用。诸如CRISPR/Cas9介导的CXCL10基因敲除技术已在临床前模型中显示出减轻肿瘤促进炎症的潜力,而基于纳米颗粒的CXCL10抑制剂可增强黑色素瘤中免疫检查点阻断的疗效。此外,靶向CXCL10相关的免疫逃逸机制(如抑制CXCR3)可能有助于预防转移。未来的研究应聚焦于在高度免疫抑制性肿瘤(如胰腺癌和胶质母细胞瘤)中靶向CXCL10的方法,在这些肿瘤中免疫检查点抑制剂已显示出有限的疗效。

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