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Macrophage-tumor cell interaction promotes ATRT progression and chemoresistance

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ARTICLE DOWNLOAD

Macrophage-tumor cell interaction promotes ATRT progression and chemoresistance

10$

Viktoria Melcher, Monika Graf, Marta Interlandi, Natalia Moreno, Flavia W. de Faria, Su Na Kim, Dennis Kastrati, Sonja Korbanka, Amelie Alfert, Joachim Gerß, Gerd Meyer zu Hörste, Wolfgang Hartmann, Michael C. Frühwald, Martin Dugas, Ulrich Schüller, Martin Hasselblatt, Thomas K. Albert & Kornelius Kerl 

Abstract

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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Year 2020
Language English
Format PDF
DOI 10.1007/s00401-019-02116-7