Evidence map›Paper›PMID 41495736›Full record

ArticleCancer cell international2026

Single-cell spatial analysis identifies ID1-high endothelial cells in tertiary lymphoid structures as predictors of durable response to immunotherapy in non-small cell lung cancer.

Kinnosuke Matsumoto, Yoshimi Noda, Kensuke Hachiya, Fumitaka Muramatsu, Naoki Okamoto, Weizhen Jia, Takayuki Shiroyama, Masahide Mori, Motohiro Tamiya, Yuhei Kinehara and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. 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

24 authors.

Kinnosuke MatsumotoDepartment of Signal Transduction, Research Institute for Microbial Diseases, the University of Osaka, 3-1 Yamadaoka, Osaka, 565-0871, Japan.
Yoshimi NodaDepartment of Signal Transduction, Research Institute for Microbial Diseases, the University of Osaka, 3-1 Yamadaoka, Osaka, 565-0871, Japan.
Kensuke HachiyaDepartment of Signal Transduction, Research Institute for Microbial Diseases, the University of Osaka, 3-1 Yamadaoka, Osaka, 565-0871, Japan.
Fumitaka MuramatsuDepartment of Signal Transduction, Research Institute for Microbial Diseases, the University of Osaka, 3-1 Yamadaoka, Osaka, 565-0871, Japan.
Naoki OkamotoDepartment of Signal Transduction, Research Institute for Microbial Diseases, the University of Osaka, 3-1 Yamadaoka, Osaka, 565-0871, Japan.
Weizhen JiaDepartment of Signal Transduction, Research Institute for Microbial Diseases, the University of Osaka, 3-1 Yamadaoka, Osaka, 565-0871, Japan.
Takayuki ShiroyamaDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, the University of Osaka , Osaka, Japan.
Masahide MoriDepartment of Thoracic Oncology, NHO Osaka Toneyama Medical Center, Osaka, Japan.
Motohiro TamiyaDepartment of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
Yuhei KineharaDepartment of Respiratory Medicine and Clinical Immunology, Nippon Life Hospital, Osaka, Japan.
Akihiro TamiyaDepartment of Internal Medicine, NHO Kinki Chuo Chest Medical Center, Osaka, Japan.
Shigeki ShimizuDepartment of Pathology, NHO Kinki Chuo Chest Medical Center, Osaka, Japan.
Hidekazu SuzukiDepartment of Thoracic Oncology, Osaka Habikino Medical Center, Osaka, Japan.
Kiyonobu UenoDepartment of Respiratory Medicine, Osaka General Medical Center, Osaka, Japan.
Toshie NikiDepartment of Respiratory Medicine, Nishinomiya Municipal Central Hospital, Hyogo, Japan.
Satoshi TetsumotoDepartment of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital, Osaka, Japan.
Osamu MorimuraDepartment of Respiratory Medicine, Toyonaka Municipal Hospital, Osaka, Japan.
Akio OsaDepartment of Respiratory Medicine, Kinki Central Hospital, Hyogo, Japan.
Toshiyuki MinamiDepartment of Respiratory Medicine and Hematology, Hyogo Medical University, Hyogo, Japan.
Satoshi NojimaDepartment of Pathology, Graduate School of Medicine, the University of Osaka , Osaka, Japan.
Yoshito TakedaDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, the University of Osaka , Osaka, Japan.
Yasushi ShintaniDepartment of General Thoracic Surgery, Graduate School of Medicine, the University of Osaka , Osaka, Japan.
Atsushi KumanogohDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, the University of Osaka , Osaka, Japan.
Nobuyuki TakakuraDepartment of Signal Transduction, Research Institute for Microbial Diseases, the University of Osaka, 3-1 Yamadaoka, Osaka, 565-0871, Japan. ntakaku@biken.osaka-u.ac.jp.

Funding

Japan Agency for Medical Research and Development 25ama221533h0002Japan Science and Technology Agency JPMJSP2138Japan Society for the Promotion of Science 20H05698Ministry of Education, Culture, Sports, Science and Technology JPMXP1323015484
6 · The paper itself

Abstract

backgroundTertiary lymphoid structures (TLSs) maturity and cellular composition shape resistance or sensitivity to immune-checkpoint blockade (ICB) across cancers. Single-cell spatial resolution data for the endothelial compartment of TLSs are lacking; therefore, we investigated the cellular composition, endothelial dynamics, and cell-cell interactions within TLS regions.

methodsWe applied high-resolution Xenium In Situ spatial transcriptomics to eight samples collected from non-small-cell lung cancers (NSCLC) (four after chemoimmunotherapy, four untreated), extracted 90 TLS regions, generated approximately 320,000 single-cell profiles from those regions, and analyzed the endothelial compartment within each TLS. We independently assessed the exploratory findings using multiplex immunofluorescence and survival analysis in a separate cohort of 45 patients receiving immunotherapy.

resultsSpatial mapping revealed a reproducible, B-cell-dominant TLS architecture across all samples. Mature TLSs contained CXCL13-rich follicular cores and were associated with a favorable prognosis. Within the endothelial compartment, high endothelial cells (HECs) forming high-endothelial venules (HEVs) segregated from other endothelial cells; in mature TLSs these HECs exhibited high inhibitor of DNA binding 1 (ID1) expression and an adhesion molecular signature, promoting lymphocyte recruitment. Patients with tumors harboring ID1-high HEVs showed higher response rates and pronounced survival advantage; multivariable analysis confirmed ID1-high status as an independent prognostic factor. Conversely, ICB exposure eventually reduced ID1 expression and adhesion molecule levels in HECs, impaired lymphocyte trafficking, and promoted a shift toward a remodeled endothelial state.

conclusionsID1expression, linked to HEC differentiation during TLS maturation or ICB exposure, marks a functionally mature, lymphocyte-recruiting HEV that predict durable response to immunotherapy. These findings provide a novel mechanistic framework and practical biomarkers for HEV-centered immuno-oncology strategies in NSCLC.

Indexed as

BiomarkerCXCL12High endothelial venulesID1ImmunotherapyNon-small-cell lung cancerRemodelingSpatial single-cell analysisSpatial transcriptomicsTertiary lymphoid structures

Identifiers

PMID41495736
PMCPMC12870244

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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.