The Tumor Microenvironment in Neuroblastoma: New Players, New Mechanisms of Interaction and New Perspectives.
The Tumor Microenvironment in Neuroblastoma: New Players, New Mechanisms of Interaction and New Perspectives.
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DOI：
10.3390/cancers12102912
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发表时间：
2020-10-10
期刊：
影响因子：
5.2
通讯作者：
DeClerck YA
中科院分区：
文献类型：
--
作者：
Blavier L;Yang RM;DeClerck YA
神经母细胞瘤是儿童中第二常见的实体瘤。在过去20年里，我们对导致神经母细胞瘤进展的遗传因素（种子）的认识有了显著提高，但肿瘤微环境（TME，土壤）的作用是近期更受关注的课题。在此，我们重点介绍近期的研究，这些研究指出了肿瘤微环境影响神经母细胞瘤进展的新机制。癌症相关成纤维细胞存在于神经母细胞瘤中，并促使肿瘤逃避化疗和免疫治疗。细胞外囊泡及其所含的调节性微小核糖核酸作为神经母细胞瘤细胞和基质细胞之间的穿梭机制。神经母细胞瘤的肿瘤微环境在MYCN扩增和MYCN未扩增的肿瘤之间存在差异，前者为“冷”肿瘤，后者为“热”肿瘤且富含炎症细胞。这些近期的观察结果将对我们设计整合神经母细胞瘤细胞及其肿瘤微环境信息的精确临床试验的能力产生重大影响。
近几十年来，肿瘤微环境（TME）对癌症进展的作用已得到广泛认可。随着癌症治疗策略日益精确且包括免疫疗法，了解肿瘤中肿瘤微环境的性质和功能变得至关重要。神经母细胞瘤是儿童中第二常见的实体瘤，我们对其肿瘤微环境的认识已从最初对施万细胞成分的关注显著发展到对其复杂性质有了更好的了解，其不仅包括免疫细胞，还包括非免疫细胞，如癌症相关成纤维细胞（CAFs），现在人们认识到它们对炎症的作用以及与肿瘤相关巨噬细胞（TAMs）的相互作用。近期对神经母细胞瘤肿瘤微环境的研究还表明，MYCN扩增（MYCN - A）和未扩增（MYCN - NA）肿瘤在基质细胞和炎症细胞含量以及免疫抑制活性方面存在显著差异。肿瘤微环境中的细胞释放的细胞外囊泡（EVs）以及其内含物中的微小核糖核酸（miRs）可能在神经母细胞瘤细胞与肿瘤微环境之间的通讯中发挥重要作用。这篇综述文章讨论了神经母细胞瘤肿瘤微环境的这些新方面，以及神经母细胞瘤肿瘤微环境信息在设计精确的、整合生物标志物的临床试验中的影响。
Neuroblastoma is the second most common solid tumor in children. Our understanding of the contribution of genetic factors (seed) that contribute to neuroblastoma progression has substantially improved in the last 2 decades but the contribution of the tumor microenvironment (TME, soil) is the subject of more recent attention. Here we highlight recent studies pointing to novel mechanisms by which the TME affects neuroblastoma progression. Cancer-associated fibroblasts are present in neuroblastoma tumors and contribute to escape from chemotherapy and immunotherapy. Extracellular vesicles and regulatory micro-RNAs they contain, serve as shuttle mechanisms between neuroblastoma cells and stromal cells. The TME landscape of neuroblastoma differs between MYCN amplified and MYCN-non amplified tumors with the former being “cold” and the latter “hot” and rich in inflammatory cells. These recent observations will have a significant impact on our ability to design precise clinical trials that integrate information on the neuroblastoma cells and on their TME. The contribution of the tumor microenvironment (TME) to cancer progression has been well recognized in recent decades. As cancer therapeutic strategies are increasingly precise and include immunotherapies, knowledge of the nature and function of the TME in a tumor becomes essential. Our understanding of the TME in neuroblastoma (NB), the second most common solid tumor in children, has significantly progressed from an initial focus on its Schwannian component to a better awareness of its complex nature, which includes not only immune but also non-immune cells such as cancer-associated fibroblasts (CAFs), the contribution of which to inflammation and interaction with tumor-associated macrophages (TAMs) is now recognized. Recent studies on the TME landscape of NB tumors also suggest significant differences between MYCN-amplified (MYCN-A) and non-amplified (MYCN-NA) tumors, in their content in stromal and inflammatory cells and their immunosuppressive activity. Extracellular vesicles (EVs) released by cells in the TME and microRNAs (miRs) present in their cargo could play important roles in the communication between NB cells and the TME. This review article discusses these new aspects of the TME in NB and the impact that information on the TME landscape in NB will have in the design of precise, biomarker-integrated clinical trials.
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影响因子：
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作者：
Erdreich-Epstein A;Singh AR;Joshi S;Vega FM;Guo P;Xu J;Groshen S;Ye W;Millard M;Campan M;Morales G;Garlich JR;Laird PW;Seeger RC;Shimada H;Durden DL
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Durden DL
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21.3
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Lyden D
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11.5
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Savoldo, Barbara
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16
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Mathivanan, Suresh
影响因子：
50.3
作者：
Becker A;Thakur BK;Weiss JM;Kim HS;Peinado H;Lyden D
通讯作者：
Lyden D