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中华临床医师杂志(电子版) ›› 2023, Vol. 17 ›› Issue (05) : 605 -613. doi: 10.3877/cma.j.issn.1674-0785.2023.05.019

综述

IL-8与肿瘤免疫的研究进展
张琪悦, 王晓东()   
  1. 100043 北京,北京大学首钢医院肿瘤内科
  • 收稿日期:2023-03-08 出版日期:2023-05-15
  • 通信作者: 王晓东

Progress in understanding of relationship between IL-8 and tumor immunity

Qiyue Zhang, Xiaodong Wang()   

  1. Department of Medical Oncology, Peking University Shougang Hospital, Beijing 100043, China
  • Received:2023-03-08 Published:2023-05-15
  • Corresponding author: Xiaodong Wang
引用本文:

张琪悦, 王晓东. IL-8与肿瘤免疫的研究进展[J/OL]. 中华临床医师杂志(电子版), 2023, 17(05): 605-613.

Qiyue Zhang, Xiaodong Wang. Progress in understanding of relationship between IL-8 and tumor immunity[J/OL]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(05): 605-613.

IL-8是最早被发现的趋化性细胞因子,在结肠癌、乳腺癌、黑色素瘤、卵巢癌等多种实体瘤中表达上调。IL-8-CXCR1/2信号通路可通过激活JAK/STAT、PI3K/Akt等多种信号通路,促进免疫抑制性细胞向肿瘤微环境的浸润、血管生成、上皮-间充质转化、干性表型的获得等过程,进一步促进肿瘤的生长、侵袭、转移及耐药性。目前认为IL-8是调节肿瘤微环境的关键因子。越来越多的研究关注IL-8-CXCR1/2信号通路相关的抗肿瘤治疗。本文就IL-8-CXCR1/2信号通路在肿瘤发生、发展、转移及免疫抑制的作用及靶向IL-8-CXCR1/2信号通路的研究进展作一综述。

Interleukin (IL)-8 is the first discovered chemotactic cytokine, and its expression is up-regulated in a variety of solid tumors such as colorectal cancer, breast cancer, melanoma, and ovarian cancer. Recent studies have shown that the IL-8-CXCR1/2 axis can promote the infiltration of immunosuppressive cells, such as myeloid-derived suppressor cells, into the tumor microenvironment, angiogenesis, epithelial-mesenchymal transition, and the acquisition of stem-like phenotypes by activating JAK/STAT, PI3K/Akt, and other signaling pathways. These signaling pathways can further promote tumor growth, invasion, metastasis, and drug resistance. Recently, IL-8 is considered to be a key factor in the regulation of the tumor microenvironment. More and more preclinical data suggest that blockade of the IL-8-CXCR1/2 axis can enhance the tumor killing function of T cells and NK cells. The combining of inhibition of the IL-8-CXCR1/2 axis with immune checkpoint inhibitors may be a promising treatment strategy for tumor. Here, we review the role of the IL-8-CXCR1/2 signaling pathway in tumor occurrence, development, metastasis, and immunosuppression, and the research and clinical trials of drugs targeting the IL-8-CXCR1/2 signaling pathway.

表1 IL-8拮抗剂相关临床试验
表2 CXCR1/2拮抗剂相关临床试验
CXCR1/2拮抗剂 文章标题 临床试验号 状态
SX-682 SX-682 Treatment in Subjects With Myelodysplastic Syndrome Who Had Disease Progression or Are Intolerant to Prior Therapy NCT04245397 R
SX-682 SX-682 Treatment in Subjects With Metastatic Melanoma Concurrently Treated With Pembrolizumab NCT03161431 R
SX-682 A Study to Evaluate the Safety and Tolerability of SX-682 in Combination With Nivolumab as a Maintenance Therapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma NCT04477343 R
瑞帕利辛 Phase Ib Pilot Study to Evaluate Reparixin in Combination with Weekly Paclitaxel in Patients with HER-2-Negative Metastatic Breast Cancer NCT02001974 C
瑞帕利辛 A randomized,placebo-controlled phase 2 study of paclitaxel in combination with reparixin compared to paclitaxel alone as front-line therapy for metastatic triple-negative breast cancer(fRida) NCT02370238C C
瑞帕利辛 A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer NCT01861054 C
AZD5069 Combination Study of AZD5069 and Enzalutamide NCT03177187 Aa
AZD5069 Study to Assess MEDI4736 With Either AZD9150 or AZD5069 in Advanced Solid Tumors & Relapsed Metastatic Squamous Cell Carcinoma of Head & Neck NCT02499328 A
AZD5069 Phase Ib/II Study of MEDI4736 Evaluated in Different Combinations in Metastatic Pancreatic Ductal Carcinoma NCT02583477 C
Navarixin Efficacy and Safety Study of Navarixin(MK-7123)in Combination With Pembrolizumab(MK-3475)in Adults With Selected Advanced/Metastatic Solid Tumors(MK-7123-034) NCT03473925 C
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