Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine.
Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana, USA.
Curr Opin Hematol. 2023 Jul 1;30(4):137-143. doi: 10.1097/MOH.0000000000000762. Epub 2023 Apr 19.
It is well described that tumor-directed aberrant myelopoiesis contributes to the generation of various myeloid populations with tumor-promoting properties. A growing number of recent studies have revealed the importance of the previously unappreciated roles of erythroid progenitor cells (EPCs) in the context of cancer, bringing the updated concept that altered erythropoiesis also facilitates tumor growth and progression. Better characterization of EPCs may provide attractive therapeutic opportunities.
EPCs represent a heterogeneous population. They exhibit crucial pro-tumor activities by secreting growth factors and modulating the immune response. Cancers induce potent EPC expansion and suppress their differentiation. Recent single-cell transcriptome and lineage tracking analyses have provided novel insight that tumor-induced EPCs are able to be transdifferentiated into immunosuppressive myeloid cells to limit T-cell function and immunotherapy. Therapeutic strategies targeting key factors of EPC-driven immunosuppression, reducing the amount of EPCs, and promoting EPC differentiation and maturation have been extensively investigated.
This review summarizes the current state of knowledge as to the fascinating biology of EPCs, highlights mechanisms by which they exert the tumor promoting activities, as well as the perspectives on future directions and strategies to target these cells for potential therapeutic benefit.
目的综述:肿瘤靶向性异常髓系细胞生成具有促肿瘤特性的各种髓系细胞已得到充分描述。越来越多的最新研究揭示了红细胞生成前体细胞 (EPCs) 在癌症背景下以前未被重视的作用的重要性,提出了更新的概念,即改变的红细胞生成也促进肿瘤生长和进展。更好地表征 EPC 可能提供有吸引力的治疗机会。
最新发现:EPC 是一个异质性群体。它们通过分泌生长因子和调节免疫反应来发挥关键的促肿瘤作用。癌症诱导强烈的 EPC 扩增并抑制其分化。最近的单细胞转录组和谱系追踪分析提供了新的见解,即肿瘤诱导的 EPC 能够转分化为免疫抑制性髓样细胞,以限制 T 细胞功能和免疫治疗。广泛研究了针对 EPC 驱动免疫抑制的关键因素的治疗策略,包括减少 EPC 的数量以及促进 EPC 分化和成熟。
总结:本文综述了 EPC 令人着迷的生物学的最新研究进展,强调了它们发挥促肿瘤作用的机制,以及针对这些细胞的未来方向和策略的观点,以期为潜在的治疗益处提供新的思路。