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Friebel, Ekaterina; Kapolou, Konstantina; Unger, Susanne; Núñez, Nicolás Gonzalo; Utz, Sebastian; Rushing, Elisabeth Jane; Regli, Luca; Weller, Michael; Greter, Melanie; Tugues, Sonia; Neidert, Marian Christoph; Becher, Burkhard
Cell, 06/2020, Letnik: 181, Številka: 7Journal Article
Brain malignancies can either originate from within the CNS (gliomas) or invade from other locations in the body (metastases). A highly immunosuppressive tumor microenvironment (TME) influences brain tumor outgrowth. Whether the TME is predominantly shaped by the 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 the leukocyte landscape of brain tumors using high-dimensional single-cell profiling (CyTOF). The heterogeneous composition of tissue-resident and invading immune cells within the TME alone permitted a clear distinction between gliomas and brain metastases (BrM). The glioma TME presented predominantly with tissue-resident, reactive microglia, whereas tissue-invading leukocytes accumulated in BrM. Tissue-invading TAMs showed a distinctive signature trajectory, revealing tumor-driven instruction along with contrasting lymphocyte activation and exhaustion. Defining the specific immunological signature of brain tumors can facilitate the rational design of targeted immunotherapy strategies. Display omitted •Leukocyte invasion is higher in brain metastasis than in CNS-endogenous cancers•The tumor type shapes the differentiation of monocyte-derived macrophages•Brain metastases harbor a high frequency of regulatory T cells•Both activation and exhaustion are prevalent in lymphocytes of the metastatic TME High-parametric single-cell mapping of the tumor microenvironment of patients with primary brain tumors or brain metastases reveals that the immune response to cancer in the brain is shaped by cancer type, with metastases favoring T cell and monocyte-derived macrophage invasion and gliomas characterized by activated microglia.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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