Journal
ACTA NEUROPATHOLOGICA
Volume 139, Issue 5, Pages 913-936Publisher
SPRINGER
DOI: 10.1007/s00401-019-02116-7
Keywords
Atypical teratoid; rhabdoid tumor; Tumor microenvironment; Tumor-associated macrophages; Single-cell RNA sequencing; Cell interaction; Chemotherapy resistance
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Atypical teratoid/rhabdoid tumors (ATRT) are known for their heterogeneity concerning pathophysiology and outcome. However, predictive factors within distinct subgroups still need to be uncovered. Using multiplex immunofluorescent staining and single-cell RNA sequencing we unraveled distinct compositions of the immunological tumor microenvironment (TME) across ATRT subgroups. CD68(+) cells predominantly infiltrate ATRT-SHH and ATRT-MYC and are a negative prognostic factor for patients' survival. Within the murine ATRT-MYC and ATRT-SHH TME, Cd68(+) macrophages are core to intercellular communication with tumor cells. In ATRT-MYC distinct tumor cell phenotypes express macrophage marker genes. These cells are involved in the acquisition of chemotherapy resistance in our relapse xenograft mouse model. In conclusion, the tumor cell-macrophage interaction contributes to ATRT-MYC heterogeneity and potentially to tumor recurrence.
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