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髓系细胞在乳腺癌进展中的作用

The Roles of Myeloid Cells in Breast Cancer Progression.

作者信息

Rivas Charlotte Helena, Liu Fengshuo, Zhang Xiang H-F

机构信息

Cancer and Cell Biology Program, Graduate School of Biomedical Sciences, San Antonio, TX, USA.

Lester and Sue Smith Breast Center, Houston, TX, USA.

出版信息

Adv Exp Med Biol. 2025;1464:397-412. doi: 10.1007/978-3-031-70875-6_19.

Abstract

This chapter reviews tumor-associated myeloid cells, including macrophages, neutrophils, and other innate immune cells, and their multifaceted roles in supporting breast cancer progression and metastasis. In primary tumors, myeloid cells play key roles in promoting tumor epithelial-mesenchymal transition (EMT) and invasion. They can facilitate intravasation (entry into the bloodstream) and colonization, disrupting the endothelial cell layer and reshaping the extracellular matrix. They can also stimulate angiogenesis, suppress immune cell responses, and enhance cancer cell adaptability. In the bloodstream, circulating myeloid cells enable the survival of disseminated tumor cells via immunosuppressive effects and physical shielding. At the metastatic sites, they prime the premetastatic niche, facilitate tumor cell extravasation, and support successful colonization and outgrowth. Mechanistically, myeloid cells enhance cancer cell survival, dormancy escape, proliferation, and mesenchymal-epithelial transition (MET). Nonetheless, substantial gaps in our understanding persist regarding the functional and spatiotemporal diversity, as well as the evolutionary patterns, of myeloid cells during metastatic progression. Myeloid cell plasticity and differential responses to therapies present key barriers to successful treatments. Identifying specific pro-tumoral myeloid cell subpopulations and disrupting their interactions with cancer cells represent promising therapeutic opportunities. Emerging evidence suggests combining immunomodulators or stromal normalizers with conventional therapies could help overcome therapy-induced immunosuppression and improve patient outcomes. Overall, further elucidating myeloid cell heterogeneity and function throughout the process of breast cancer progression and metastasis will enable more effective therapeutic targeting of these critical stromal cells.

摘要

本章回顾了肿瘤相关髓系细胞,包括巨噬细胞、中性粒细胞和其他固有免疫细胞,以及它们在支持乳腺癌进展和转移中所起的多方面作用。在原发性肿瘤中,髓系细胞在促进肿瘤上皮-间质转化(EMT)和侵袭方面发挥关键作用。它们可以促进肿瘤细胞进入血管(进入血流)和定植,破坏内皮细胞层并重塑细胞外基质。它们还可以刺激血管生成,抑制免疫细胞反应,并增强癌细胞的适应性。在血流中,循环髓系细胞通过免疫抑制作用和物理屏障使播散的肿瘤细胞得以存活。在转移部位,它们为前转移微环境做准备,促进肿瘤细胞外渗,并支持成功的定植和生长。从机制上讲,髓系细胞可增强癌细胞的存活、休眠逃逸、增殖以及间质-上皮转化(MET)。尽管如此,我们对髓系细胞在转移进展过程中的功能和时空多样性以及进化模式的理解仍存在很大差距。髓系细胞的可塑性和对治疗的不同反应是成功治疗的关键障碍。识别特定的促肿瘤髓系细胞亚群并破坏它们与癌细胞的相互作用代表了有前景的治疗机会。新出现的证据表明,将免疫调节剂或基质调节剂与传统疗法相结合可能有助于克服治疗引起的免疫抑制并改善患者预后。总体而言,进一步阐明乳腺癌进展和转移过程中髓系细胞的异质性和功能,将能够更有效地靶向这些关键的基质细胞进行治疗。

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