Evidence map›Paper›PMID 42414284›Full record

ArticleNature communications2026

Anti-PD-1 plus anti-CTLA-4 blockade overcomes immune exclusion in NSCLC brain metastases by enhancing CD8

Kazutaka Hosoya, Hiroaki Ozasa, Takahiro Tsuji, Masahiro Oi, Yusuke Shima, Keiichiro Suminaga, Kentaro Hashimoto, Hiroshi Yoshida, Tomoko Funazo, Hitomi Ajimizu and 13 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

23 authors.

Kazutaka HosoyaDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID 0000-0002-7864-897X
Hiroaki OzasaDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. ozahiro@kuhp.kyoto-u.ac.jp.ORCID 0000-0002-5315-3751
Takahiro TsujiDepartment of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0000-0002-5706-8300
Masahiro OiDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yusuke ShimaDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Keiichiro SuminagaDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Kentaro HashimotoDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID 0000-0002-3116-2411
Hiroshi YoshidaDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Tomoko FunazoDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID 0000-0003-2152-2150
Hitomi AjimizuDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Takashi NomizoDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID 0000-0002-4328-3042
Hironori YoshidaDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hiroyuki KatsuragawaDepartment of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Kentaro TsujiDepartment of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Noritaka SanoDepartment of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Shigeki TakadaDepartment of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID 0000-0003-2977-888X
Yohei MineharuDepartment of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID 0000-0002-6346-3999
Shigeto NishikawaDepartment of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Toshi MenjuDepartment of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Akihiko YoshizawaDepartment of Diagnostic Pathology, Nara Medical University, Kashihara, Japan.ORCID 0000-0003-1462-7341
Yoshiki ArakawaDepartment of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID 0000-0003-4626-4645
Hiroaki WakeDepartment of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Toyohiro HiraiDepartment of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Brain metastases (BrMs) in non-small cell lung cancer (NSCLC) respond poorly to anti-PD-1 monotherapy, but the underlying immune resistance remains incompletely defined. Here we integrate clinical outcome analyses, paired human tissue profiling and syngeneic mouse models to characterize the BrM immune microenvironment. Clinical analyses suggest improved intracranial disease control with nivolumab plus ipilimumab compared with nivolumab alone. Paired human specimens show that BrMs contain fewer cytotoxic T lymphocytes (CTLs) and tertiary lymphoid structures (TLSs) than primary tumors, defining an immune-excluded phenotype. A syngeneic BrM model recapitulates this phenotype and resists anti-PD-1 monotherapy, whereas combined anti-PD-1 and anti-CTLA-4 blockade suppresses tumor growth and prolongs survival. Single-cell RNA sequencing, flow cytometry and immunofluorescence show increased CTL infiltration and effector function after combination therapy. CD8

Indexed as

Brain NeoplasmsCarcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesCTLA-4 AntigenImmune Checkpoint InhibitorsLung NeoplasmsProgrammed Cell Death 1 ReceptorTertiary Lymphoid StructuresAnimalsCell Line, TumorFemaleHumansIpilimumabMiceMice, Inbred C57BLT-Lymphocytes, CytotoxicCTLA-4 AntigenCTLA4 protein, humanImmune Checkpoint InhibitorsIpilimumabPDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID42414284
PMCPMC13342341

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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.