小柯机器人

瑞士洛桑大学Johanna A. Joyce团队近期取得重要工作进展，他们通过对脑转移中内皮细胞和壁细胞的研究，揭示了关键的免疫调节机制。相关研究成果2024年1月18日在线发表于《癌细胞》杂志上。

据介绍，脑转移瘤(BrM)是一种常见的恶性肿瘤，主要来源于肺癌、黑色素瘤和乳腺癌。血管系统是BrM肿瘤微环境的关键组成部分，在调节转移的发生和进展中起着关键作用。然而，对BrM主要血管成分，即内皮细胞和壁细胞的异质性仍知之甚少。

研究人员对分类的血管细胞类型进行单细胞和大量RNA测序，并检测与非肿瘤脑相比特异性富集BrM的多种亚型（包括以前未识别的免疫调节亚型）。研究人员将人类数据与小鼠模型相结合，创建了一个BrM治疗血管靶点的查询平台。研究人员发现，CD276免疫检查点分子在BrM血管系统中显著上调，抗CD276阻断抗体在临床前试验中延长了生存期。

总之，这项研究为血管之间复杂的相互作用提供了重要的见解。

附：英文原文

Title: Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms

Author: Leire Bejarano, Annamaria Kauzlaric, Eleni Lamprou, Joao Lourenco, Nadine Fournier, Michelle Ballabio, Roberto Colotti, Roeltje Maas, Sabine Galland, Matteo Massara, Klara Soukup, Johanna Lilja, Jean-Philippe Brouland, Andreas F. Hottinger, Roy T. Daniel, Monika E. Hegi, Johanna A. Joyce

Issue&Volume: 2024-01-18

Abstract: Brain metastasis (BrM) is a common malignancy, predominantly originating from lung, melanoma, and breast cancers. The vasculature is a key component of the BrM tumor microenvironment with critical roles in regulating metastatic seeding and progression. However, the heterogeneity of the major BrM vascular components, namely endothelial and mural cells, is still poorly understood. We perform single-cell and bulk RNA-sequencing of sorted vascular cell types and detect multiple subtypes enriched specifically in BrM compared to non-tumor brain, including previously unrecognized immune regulatory subtypes. We integrate the human data with mouse models, creating a platform to interrogate vascular targets for the treatment of BrM. We find that the CD276 immune checkpoint molecule is significantly upregulated in the BrM vasculature, and anti-CD276 blocking antibodies prolonged survival in preclinical trials. This study provides important insights into the complex interactions between the vasculature, immune cells, and cancer cells, with translational relevance for designing therapeutic interventions.

DOI: 10.1016/j.ccell.2023.12.018

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00446-4

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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