Madkhali Osama A, Moni Sivakumar S, Almoshari Yosif, Sabei Fahad Y, Safhi Awaji Y
Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.
Health Research Centre, Jazan University, Jazan, Saudi Arabia.
Cancer Biol Ther. 2025 Dec;26(1):2538962. doi: 10.1080/15384047.2025.2538962. Epub 2025 Aug 4.
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.
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。