近日，瑞士苏黎世大学Burkhard Becher小组绘制出人类脑癌的单细胞图谱，从而揭示了组织侵袭性白细胞的肿瘤特异性。该项研究成果于2020年5月28日在线发表在《细胞》杂志上。

研究人员使用高维单细胞分析（CyTOF）绘制了脑肿瘤的白细胞分布图谱。仅在肿瘤微环境（TME）中，组织驻留和侵袭性免疫细胞的异质成分就使脑胶质瘤和脑转移瘤（BrM）有了明显的区别。胶质瘤TME主要表现为组织驻留性反应性小胶质细胞，而侵袭组织的白细胞则聚集在BrM中。

侵入组织的肿瘤相关巨噬细胞（TAM）显示出独特的特征轨迹，揭示了肿瘤驱动的信号以及淋巴细胞的激活和耗竭。因此，定义脑肿瘤的特异性免疫学特征可以促进靶向免疫治疗策略的设计。

据悉，脑部恶性肿瘤可能起源于中枢神经系统（神经胶质瘤），也可能起源于身体其他部位（转移）。高度免疫抑制的TME影响脑肿瘤的生长。TME是主要由中枢神经系统微环境还是由恶性肿瘤本身形成，以及与中枢神经系统TAM的多样性、起源和功能之间的联系尚不清楚。

附：英文原文

Title: Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specific Instruction of Tissue-Invading Leukocytes

Author: Ekaterina Friebel, Konstantina Kapolou, Susanne Unger, Nicolás Gonzalo Núez, Sebastian Utz, Elisabeth Jane Rushing, Luca Regli, Michael Weller, Melanie Greter, Sonia Tugues, Marian Christoph Neidert, Burkhard Becher

Issue&Volume: 2020-05-28

Abstract: Brain malignancies can either originate from within the CNS (gliomas) or invade fromother locations in the body (metastases). A highly immunosuppressive tumor microenvironment(TME) influences brain tumor outgrowth. Whether the TME is predominantly shaped bythe CNS micromilieu or by the malignancy itself is unknown, as is the diversity, origin,and function of CNS tumor-associated macrophages (TAMs). Here, we have mapped theleukocyte landscape of brain tumors using high-dimensional single-cell profiling (CyTOF).The heterogeneous composition of tissue-resident and invading immune cells withinthe TME alone permitted a clear distinction between gliomas and brain metastases (BrM).The glioma TME presented predominantly with tissue-resident, reactive microglia, whereastissue-invading leukocytes accumulated in BrM. Tissue-invading TAMs showed a distinctivesignature trajectory, revealing tumor-driven instruction along with contrasting lymphocyteactivation and exhaustion. Defining the specific immunological signature of braintumors can facilitate the rational design of targeted immunotherapy strategies.

DOI: 10.1016/j.cell.2020.04.055

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30561-4