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单核细胞,乳腺癌肿瘤微环境(TME)中的指挥家。

The Monocyte, a Maestro in the Tumor Microenvironment (TME) of Breast Cancer.

作者信息

Amer Hoda T, Stein Ulrike, El Tayebi Hend M

机构信息

Molecular Pharmacology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11865, Egypt.

Translational Oncology of Solid Tumors, Experimental and Clinical Research Center, Charité-Universitäsmedizin Berlin and Max-Delbrük-Center for Molecular Medicine in the Helmholtz Association, 10117 Berlin, Germany.

出版信息

Cancers (Basel). 2022 Nov 7;14(21):5460. doi: 10.3390/cancers14215460.

Abstract

Breast cancer (BC) is well-known for being a leading cause of death worldwide. It is classified molecularly into luminal A, luminal B HER2-, luminal B HER2+, HER2+, and triple-negative breast cancer (TNBC). These subtypes differ in their prognosis; thus, understanding the tumor microenvironment (TME) makes new treatment strategies possible. The TME contains populations that exhibit anti-tumorigenic actions such as tumor-associated eosinophils. Moreover, it contains pro-tumorigenic populations such as tumor-associated neutrophils (TANs), or monocyte-derived populations. The monocyte-derived populations are tumor-associated macrophages (TAMs) and MDSCs. Thus, a monocyte can be considered a maestro within the TME. Moreover, the expansion of monocytes in the TME depends on many factors such as the BC stage, the presence of macrophage colony-stimulating factor (M-CSF), and the presence of some chemoattractants. After expansion, monocytes can differentiate into pro-inflammatory populations such as M1 macrophages or anti-inflammatory populations such as M2 macrophages according to the nature of cytokines present in the TME. Differentiation to TAMs depends on various factors such as the BC subtype, the presence of anti-inflammatory cytokines, and epigenetic factors. Furthermore, TAMs and MDSCs not only have a role in tumor progression but also are key players in metastasis. Thus, understanding the monocytes further can introduce new target therapies.

摘要

乳腺癌(BC)是全球主要的死亡原因之一,广为人知。它在分子水平上被分为腔面A型、腔面B型HER2阴性、腔面B型HER2阳性、HER2阳性和三阴性乳腺癌(TNBC)。这些亚型的预后不同;因此,了解肿瘤微环境(TME)有助于制定新的治疗策略。TME中存在具有抗肿瘤作用的细胞群体,如肿瘤相关嗜酸性粒细胞。此外,它还包含促肿瘤细胞群体,如肿瘤相关中性粒细胞(TANs)或单核细胞衍生群体。单核细胞衍生群体包括肿瘤相关巨噬细胞(TAMs)和髓源性抑制细胞(MDSCs)。因此,单核细胞可被视为TME中的“指挥家”。此外,TME中单核细胞的扩增取决于许多因素,如BC分期、巨噬细胞集落刺激因子(M-CSF)的存在以及某些趋化因子的存在。扩增后,单核细胞可根据TME中细胞因子的性质分化为促炎细胞群体,如M1巨噬细胞,或抗炎细胞群体,如M2巨噬细胞。向TAMs的分化取决于多种因素,如BC亚型、抗炎细胞因子的存在和表观遗传因素。此外,TAMs和MDSCs不仅在肿瘤进展中起作用,而且在转移中也是关键因素。因此,进一步了解单核细胞可以引入新的靶向治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba1/9658645/acaf89d93596/cancers-14-05460-g001.jpg

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