CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：The Importance of Chemokines Activating CXCR1, CXCR2 and CXCR3 in Tumorigenesis as Potential Therapeutic Targets in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma.
The Importance of Chemokines Activating CXCR1, CXCR2 and CXCR3 in Tumorigenesis as Potential Therapeutic Targets in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma.
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多发性骨髓瘤（MM）是一种浆细胞肿瘤。尽管治疗方法日益先进，多发性骨髓瘤仍然难以完全治愈。因此，人们正在研究这种肿瘤的潜在机制，以确定新的治疗靶点并理解化疗耐药性。特别关注的是MM骨髓微环境，其中趋化因子是其关键组成部分之一。本综述探讨了激活CXCR2和CXCR3受体的趋化因子在意义未明的单克隆丙种球蛋白病（MGUS）和MM中的作用，重点介绍了所有CXC趋化因子及其受体，包括CXCL1、CXCL8/IL-8、CXCL9、CXCL10和血小板因子4。
我们关注选定的CXC趋化因子对MM细胞的直接作用，特别是它们在增殖、迁移、与骨髓细胞相互作用、髓外疾病形成和化疗耐药性中的作用。
此外，我们探讨了这些趋化因子对MM骨髓微环境的影响，特别是与间充质基质细胞、髓源性抑制细胞、破骨细胞、M2巨噬细胞和NK 细胞的关系，以及骨破坏和血管生成等过程。
最后，我们讨论了靶向上述两个趋化因子轴的药物的潜在用途，重点关注抑制剂和过继性细胞疗法。
Multiple myeloma (MM) is a neoplasm of plasma cells. Despite the development of increasingly advanced treatments, multiple myeloma remains challenging to cure completely. Consequently, the underlying mechanisms of this neoplasm are being investigated to identify new therapeutic targets and understand chemoresistance.
A particular focus has been placed on the MM bone marrow microenvironment, with chemokines being one of its key components. This review examines the role of chemokines that activate the CXCR2 and CXCR3 receptors in both monoclonal gammopathy of undetermined significance (MGUS) and MM, highlighting all CXC chemokines and their receptors, including CXCL1, CXCL8/IL-8, CXCL9, CXCL10, and platelet factor 4.
We focus on the direct effects of selected CXC chemokines on MM cells, specifically their roles in proliferation, migration, interaction with bone marrow cells, the formation of extramedullary disease, and chemoresistance.
Additionally, we explore the impact of these chemokines on the MM bone marrow microenvironment, particularly in relation to mesenchymal stromal cells, myeloid-derived suppressor cells, osteoclasts, M2 macrophages, and natural killer cells, as well as processes such as bone destruction and angiogenesis.
Finally, we discuss the potential use of drugs targeting the two chemokine axes described, with a focus on inhibitors and adoptive cell therapy.
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