OSCR

Brain metastases exhibit distinct spatial patterns of resident and infiltrating macrophages.

Overview

Authors: Avinoam Ratzabi1, Itai M. Caspit1,2, Ira Telechi1,2, Jung-Seok Kim3, Hananya Vaknine4, Pablo Blinder1,2, Steffen Jung3, Reuven Stein1,2
ORCID iDs: Jung-Seok Kim, Pablo Blinder, Steffen Jung, Reuven Stein
  1. Department of Neurobiology, School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University,Tel Aviv, Israel
  2. Sagol School of Neuroscience, Tel Aviv University,Tel Aviv, Israel
  3. Department of Immunology and Regenerative Biology, Weizmann Institute of Science,Rehovot, Israel
  4. Institute of Pathology, E. Wolfson Medical Center,Holon, Israel
Institutions: Tel Aviv University (Israel); Weizmann Institute of Science (Israel); Wolfson Medical Center (Israel)
Journal: Cell death discovery, volume 12, issue 1, article 211
Dates: received 6 December 2025; accepted 12 March 2026; published online 1 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41420-026-03084-0 · PMID 41916966 · PMCID PMC13168416 · OpenAlex W7147312804
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: other condition (population)
Methods: Statistics, Evoked potentials, Connectivity
Keywords: CNS cancer, Neuroimmunology
Topic: Brain Metastases and Treatment (Pulmonary and Respiratory Medicine, Medicine), according to OpenAlex
Funding: Israel Science Foundation (ISF) (1125/20); Israel Cancer Research Fund (Israel Cancer Research Fund, Inc.) (24-113-PG); Prajs-Drimmer institute for the development of anti-degenerative drugs
Citations: cited by 1 paper (Europe PMC); 75 references in the paper
Research resources: RRID:IMSR_JAX:021160, RRID:SCR_008520

Abstract

Brain metastases (BrM) are a leading cause of morbidity and mortality, arising in multiple brain compartments. BrM colonization and progression are shaped by interactions with distinct tumor-associated macrophage (TAM) subsets, including microglia (MG), monocyte-derived macrophages (MDM), and border-associated macrophages (BAM). While transcriptomes of TAM have been characterized in detail, their spatial distribution, abundance, and compartment-specific composition -particularly in relation to BrM size and the cancer origin—remain poorly defined. Here, we performed a comprehensive spatial analysis of TAM subtypes across brain regions using experimental BrM models of lung and breast cancer, as well as melanoma. We distinguished TAM subsets by both origin and location, employing genetically traceable mouse models. We observed expansion of MG and BAM, as well as MDM infiltration associated with BrM, albeit with distinct compositions. Parenchymal BrM contained both MG and MDM, whereas ventricular and leptomeningeal BrM contained BAM and MDM but lacked MG. TAM abundance varied with BrM size, compartment, and cancer type: MG predominated in early parenchymal lesions, with MDM becoming dominant as tumors grew. Notably, melanoma BrM exhibited markedly reduced MDM infiltration compared with lung and breast cancer BrM. These findings highlight the need to tailor TAM-targeted therapies not only to the primary tumor type but also to the brain compartment affected. A deeper understanding of TAM dynamics across compartments may improve the precision and efficacy of BrM treatments.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

Code availability

The custom code/scripts used in this study are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Tracing map

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Data

No dataset and no data link were found in the paper.

Data availability

Data will be made available on reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 2 keywords, 3 funders, 75 references, 2 RRIDs.

Cite

This paper

Ratzabi, A., Caspit, I. M., Telechi, I., Kim, J.-S., Vaknine, H., Blinder, P., Jung, S., & Stein, R. (2026). Brain metastases exhibit distinct spatial patterns of resident and infiltrating macrophages. Cell death discovery, 12(1), 211. https://doi.org/10.1038/s41420-026-03084-0

BibTeX

@article{ratzabi2026brain,
author = {Ratzabi, Avinoam and Caspit, Itai M. and Telechi, Ira and Kim, Jung-Seok and Vaknine, Hananya and Blinder, Pablo and Jung, Steffen and Stein, Reuven},
title = {{Brain metastases exhibit distinct spatial patterns of resident and infiltrating macrophages}},
journal = {Cell death discovery},
year = {2026},
month = apr,
volume = {12},
number = {1},
pages = {211},
publisher = {Nature Publishing Group},
issn = {2058-7716},
doi = {10.1038/s41420-026-03084-0},
url = {https://doi.org/10.1038/s41420-026-03084-0},
pmid = {41916966},
pmcid = {PMC13168416}
}

RIS

TY - JOUR
AU - Ratzabi, Avinoam
AU - Caspit, Itai M.
AU - Telechi, Ira
AU - Kim, Jung-Seok
AU - Vaknine, Hananya
AU - Blinder, Pablo
AU - Jung, Steffen
AU - Stein, Reuven
TI - Brain metastases exhibit distinct spatial patterns of resident and infiltrating macrophages
T2 - Cell death discovery
J2 - Cell Death Discov
PY - 2026
DA - 2026/04/01
VL - 12
IS - 1
SP - 211
SN - 2058-7716
PB - Nature Publishing Group
DO - 10.1038/s41420-026-03084-0
UR - https://doi.org/10.1038/s41420-026-03084-0
LA - en
ER -

CSL-JSON

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