TAMs in brain metastasis: molecular signatures in mouse and man

  • Macrophages not only represent an integral part of innate immunity but also critically contribute to tissue and organ homeostasis. Moreover, disease progression is accompanied by macrophage accumulation in many cancer types and is often associated with poor prognosis and therapy resistance. Given their critical role in modulating tumor immunity in primary and metastatic brain cancers, macrophages are emerging as promising therapeutic targets. Different types of macrophages infiltrate brain cancers, including (i) CNS resident macrophages that comprise microglia (TAM-MG) as well as border-associated macrophages and (ii) monocyte-derived macrophages (TAM-MDM) that are recruited from the periphery. Controversy remained about their disease-associated functions since classical approaches did not reliably distinguish between macrophage subpopulations. Recent conceptual and technological advances, such as large-scale omic approaches, provided new insight into molecular profiles of TAMs based on their cellular origin. In this review, we summarize insight from recent studies highlighting similarities and differences of TAM-MG and TAM-MDM at the molecular level. We will focus on data obtained from RNA sequencing and mass cytometry approaches. Together, this knowledge significantly contributes to our understanding of transcriptional and translational programs that define disease-associated TAM functions. Cross-species meta-analyses will further help to evaluate the translational significance of preclinical findings as part of the effort to identify candidates for macrophage-targeted therapy against brain metastasis.

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Author:Michael SchulzGND, Lisa SevenichORCiDGND
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Document Type:Article
Date of Publication (online):2021/09/03
Date of first Publication:2021/09/03
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2021/09/29
Tag:brain cancer; cerebral metastasis; microglia; targeted therapy; tumor immunology; tumor microenvironment; tumor-associated macrophages
Issue:art. 716504
Page Number:16
First Page:1
Last Page:16
Research in the lab of LS is supported by institutional funds from the Georg-Speyer-Haus jointly funded by the German Federal Ministry of Health and the Ministry of Higher Education, Research and the Arts of the State of Hesse (HMWK), as well as grants from the German Cancer Aid (Max-Eder Junior Group Leader Program 70111752) and German Research Foundation (SE2234/3-1).
Biowissenschaften / Biowissenschaften
Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0