Publikation

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

Wissenschaftlicher Artikel/Review - 28.05.2020

Bereiche
PubMed
DOI

Zitation
Friebel E, Neidert M, Tugues S, Greter M, Weller M, Regli L, Rushing E, Utz S, Núñez N, Unger S, Kapolou K, Becher B. Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specific Instruction of Tissue-Invading Leukocytes. Cell 2020; 181:1626-1642.e20.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Cell 2020; 181
Veröffentlichungsdatum
28.05.2020
eISSN (Online)
1097-4172
Seiten
1626-1642.e20
Kurzbeschreibung/Zielsetzung

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.