Soto Manuel Sarmiento, Sibson Nicola R
Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom.
Department of Biochemistry and Molecular Biology, University of Seville, Seville, Spain.
Front Cell Neurosci. 2018 Nov 12;12:414. doi: 10.3389/fncel.2018.00414. eCollection 2018.
The immune landscape in brain metastasis is a very heterogeneous framework. Amongst a broad plethora of cells within the tumor microenvironment, the presence of activated microglia has been perfectly described. The innate role of microglial cells is to detect and eliminate any insults that may disturb the regular behavior of the brain. As part of its defensive role, it releases pro- and anti-inflammatory cytokines that aim to modulate the inflammatory scenario at the metastatic . However, the long term effects that these cells may exert on the metastatic progression is not clear. One of the biggest challenges in the field is to distinguish between brain resident microglial cells and infiltrated bone-marrow derived macrophages. Part of this issue is the fact that both cell types share similar phenotypes. Current studies are based on the modulation of the immune response against cancer cells (immunotherapy). However, most of current clinical trials and newly developed drugs focus on the adaptive immune response (e.g., immune blockade check-points). Additionally, the unique structure of the central nervous system with the presence of the blood-brain barrier have hindered a significant advance in novel therapies against brain metastasis. In this manuscript, we describe current advances in characterization of tumor-associated microglia and macrophages, the importance of microglia during the anti-cancerous response, and the future direction for the development of new strategies against this complex disease.
脑转移瘤中的免疫格局是一个非常异质性的框架。在肿瘤微环境中种类繁多的细胞中，活化小胶质细胞的存在已得到充分描述。小胶质细胞的固有作用是检测和消除任何可能干扰大脑正常行为的损伤。作为其防御作用的一部分，它会释放促炎和抗炎细胞因子，旨在调节转移部位的炎症情况。然而，这些细胞对转移进展可能产生的长期影响尚不清楚。该领域最大的挑战之一是区分脑内常驻小胶质细胞和浸润的骨髓来源巨噬细胞。部分问题在于这两种细胞类型具有相似的表型。当前的研究基于对癌细胞免疫反应的调节（免疫疗法）。然而，目前大多数临床试验和新开发的药物都集中在适应性免疫反应（例如免疫阻断检查点）上。此外，存在血脑屏障的中枢神经系统的独特结构阻碍了针对脑转移瘤的新疗法取得重大进展。在本手稿中，我们描述了肿瘤相关小胶质细胞和巨噬细胞表征的当前进展、小胶质细胞在抗癌反应中的重要性以及针对这种复杂疾病的新策略开发的未来方向。
