2019
DOI: 10.1007/s00401-019-02116-7
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Macrophage-tumor cell interaction promotes ATRT progression and chemoresistance

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 muri… Show more

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Cited by 29 publications
(39 citation statements)
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“…TAMs can also produce factors that promote tumor growth, angiogenesis, and metastasis (Lee et al, 2018;Maximov et al, 2019). Studies in many types of solid tumors show that TAMs are heterogeneous and their composition varies among tumors (Alshetaiwi et al, 2020;Gubin et al, 2018;Melcher et al, 2020). Despite increasing interest in TAMs as therapeutic targets, most studies have been performed on tumors outside the brain.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…TAMs can also produce factors that promote tumor growth, angiogenesis, and metastasis (Lee et al, 2018;Maximov et al, 2019). Studies in many types of solid tumors show that TAMs are heterogeneous and their composition varies among tumors (Alshetaiwi et al, 2020;Gubin et al, 2018;Melcher et al, 2020). Despite increasing interest in TAMs as therapeutic targets, most studies have been performed on tumors outside the brain.…”
Section: Discussionmentioning
confidence: 99%
“…Finally, we wished to compare our scRNA-seq findings to another brain tumor model, selecting scRNA-seq data from a mouse model of an atypical teratoid rhabdoid tumor (ATRT) (Melcher et al, 2020). Like MB, ATRT is an embryonal tumor.…”
Section: Ontogeny and Microenvironment Influence Tam Gene Expressionmentioning
confidence: 99%
“…This chemoresistance may be produced by the tumor host factors [103] or factors associated with tumor-tumor microenvironment interactions [104]. The implication of the tumor microenvironment on the progression of the tumor and the chemoresistance nowadays is widely recognized [105][106][107][108][109][110]. The tumor microenvironment consists of tumor cells, vasculature, extracellular matrix (ECM), non-malignant cells, such as, stromal cells, tumor associated fibroblast (CAFs), immune cells and a complex signaling molecule network which include growth factors, cytokines, chemokines, and exosomes that sustain the internal connections of the microenvironment, [111,112].…”
Section: The Antitumor Effect In Preclinical In Vitro and In Vivo Modmentioning
confidence: 99%
“…Similar to other pediatric tumors, the immune infiltrate composition corresponds with the molecular subtype. Macrophages predominantly infiltrate the ATRT-SHH and ATRT-MYC subtypes and correlate with poor prognosis and treatment resistance ( 109 ). These data again indicate that therapeutic strategies must take into account the subtype classification and its respective immune microenvironment properties in pediatric brain tumors.…”
Section: Pediatric Brain Tumorsmentioning
confidence: 99%