Evidence map›Paper›PMID 42171608›Full record

ArticleJCI insight2026

Distinct immune landscapes characterize highly versus minimally invasive brain metastases.

Sarah M Maritan, Elham Karimi, Matthew Dankner, Aldo Hernandez-Corchado, Miranda W Yu, Matthew G Annis, Yashar Aghazadeh Habashi, Morteza Rezanejad, Bridget Liu, Nebras Koudieh and 15 more

Abstract read
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Sarah M MaritanGoodman Cancer Institute.
Elham KarimiGoodman Cancer Institute.
Matthew DanknerGoodman Cancer Institute.
Aldo Hernandez-CorchadoDepartment of Human Genetics, Faculty of Medicine and Health Sciences.
Miranda W YuGoodman Cancer Institute.
Matthew G AnnisGoodman Cancer Institute.
Yashar Aghazadeh HabashiGoodman Cancer Institute.
Morteza RezanejadGoodman Cancer Institute.
Bridget LiuGoodman Cancer Institute.
Nebras KoudiehResearch Institute of McGill University Health Centre, Montreal, Quebec, Canada.
Emilie PichetteDepartment of Pathology, Faculty of Medicine and Health Sciences, and.
Parvaneh FallahGerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.
Benoit FisetGoodman Cancer Institute.
Yuhong WeiGoodman Cancer Institute.
Ali NehmeVictor Phillip Dahdaleh Institute of Genomic Medicine, and.
Chun Geun LeeIntercollege, Hanyang University, Seoul, Korea.
Jack A EliasDivision of Medicine and Biological Sciences, Brown University, Providence, Rhode Island, USA.
Morag ParkGoodman Cancer Institute.
Yasser RiazalhosseiniDepartment of Human Genetics, Faculty of Medicine and Health Sciences.
Hamed NajafabadiDepartment of Human Genetics, Faculty of Medicine and Health Sciences.
Kevin PetreccaMontreal Neurological Institute-Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
Marie-Christine GuiotDepartment of Pathology, Faculty of Medicine and Health Sciences, and.
Daniela F QuailGoodman Cancer Institute.
Logan A WalshGoodman Cancer Institute.
Peter M SiegelGoodman Cancer Institute.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Brain metastases (BrMs) occur in approximately 30% of cancer patients, causing nearly one-fifth of cancer deaths. While immune checkpoint inhibitors (ICIs) benefit some BrM patients, responses remain highly variable. This variability partly reflects distinct histopathological growth patterns that include minimally invasive (MI) and highly invasive (HI) brain BrMs. Here we show that MI BrMs exhibit robust immune infiltration, whereas HI lesions are immunosuppressed. However, histological differentiation between MI and HI can be challenging because of subjective margin assessment. Here, using highly multiplexed spatial proteomics on 119 tumor sections from 46 patients with BrMs, we identify CHI3L1 as a key mediator of the immunosuppressive microenvironment in HI BrMs. In preclinical models, genetic deletion of CHI3L1 converts immune-cold metastases into lymphocyte-rich, ICI-responsive lesions infiltrated by granzyme B+ CD8+ T cells. In BrM patients treated with ICI, immunohistochemical quantification of CHI3L1 expression was a stronger predictor of ICI response than traditional MI/HI classification. Thus, CHI3L1 represents a promising biomarker and therapeutic target for BrMs.

Indexed as

Brain NeoplasmsChitinase-3-Like Protein 1AnimalsBiomarkers, TumorCD8-Positive T-LymphocytesFemaleGranzymesHumansImmune Checkpoint InhibitorsMaleMiceProteomicsTumor MicroenvironmentBiomarkers, TumorChitinase-3-Like Protein 1GranzymesImmune Checkpoint InhibitorsBrain cancerImmunologyOncology

Identifiers

PMID42171608
PMCPMC13232719

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.