Evidence map›Paper›PMID 40866351›Full record

ArticleNature communications2025

Clonal diversity shapes the tumour microenvironment leading to distinct immunotherapy responses in metastatic urothelial carcinoma.

Takashi Kamatani, Kota Umeda, Tomohiro Iwasawa, Fuyuki Miya, Kazuhiro Matsumoto, Shuji Mikami, Kensuke Hara, Masayuki Shimoda, Yutaka Suzuki, Jo Nishino and 5 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
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

15 authors.

Takashi Kamatani *Department of AI Technology Development, M&D Data Science Center, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
Kota Umeda *Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Tomohiro IwasawaDepartment of Urology, Keio University School of Medicine, Tokyo, Japan.
Fuyuki MiyaCenter for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.ORCID http://orcid.org/0000-0001-6758-2015
Kazuhiro MatsumotoDepartment of Urology, Keio University School of Medicine, Tokyo, Japan.ORCID http://orcid.org/0000-0001-9222-0999
Shuji MikamiDepartment of Diagnostic Pathology, National Hospital Organization Saitama Hospital, Saitama, Japan.
Kensuke HaraDepartment of Pathology, Keio University School of Medicine, Tokyo, Japan.
Masayuki ShimodaDepartment of Pathology, Keio University School of Medicine, Tokyo, Japan.
Yutaka SuzukiDepartment of Computational Biology and Medical Sciences, The University of Tokyo, Chiba, Japan.ORCID http://orcid.org/0000-0003-4852-1879
Jo NishinoDivision of Bioinformatics, Research Institute, National Cancer Center Japan, Tokyo, Japan.
Mamoru KatoDivision of Bioinformatics, Research Institute, National Cancer Center Japan, Tokyo, Japan.ORCID http://orcid.org/0000-0002-8485-8316
Kazuhiro KakimiDepartment of Immunology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.ORCID http://orcid.org/0000-0003-2631-3040
Nobuyuki TanakaDepartment of Urology, Keio University School of Medicine, Tokyo, Japan. urotanaka@keio.jp.ORCID http://orcid.org/0000-0003-0841-9167
Mototsugu OyaDepartment of Urology, Keio University School of Medicine, Tokyo, Japan. moto-oya@keio.jp.
Tatsuhiko TsunodaLaboratory for Medical Science Mathematics, Department of Biological Sciences, School of Science, The University of Tokyo, Tokyo, Japan. tsunoda@bs.s.u-tokyo.ac.jp.ORCID http://orcid.org/0000-0002-5439-7918

Funding

MEXT | Japan Science and Technology Agency (JST) JPMJCR2231MEXT | Japan Science and Technology Agency (JST) JPMJMS2217MEXT | Japan Society for the Promotion of Science (JSPS) 20H03240, 25K02261MEXT | Japan Society for the Promotion of Science (JSPS) 20K16408, 22K15576MEXT | Japan Society for the Promotion of Science (JSPS) 21K19414, 22H03217, 23K24476, 24K21301MEXT | Japan Society for the Promotion of Science (JSPS) 23K08724MEXT | Japan Society for the Promotion of Science (JSPS) 24H00649
6 · The paper itself

Abstract

Repeated oncogenic mutations and polyclonal proliferation are evident in cancers. However, little is known about the polyclonal principles governing the systemic cancerous lineage during immunotherapy. Here, we examine a unique autopsy case of metastatic urothelial carcinoma that exhibits different treatment responses to anti-PD-1 therapy at each tumor site. By performing in-depth analyses of different multiregional bulk tumor masses, we reveal that subsets of subclones acquire potential driver mutations under treatment selection pressure. Spatial transcriptomics analysis reveals that subclones resistant to immunotherapy form distinct immunosuppressive environments consistent with their habitats. Furthermore, different cancer hallmarks are identified in each of the subclones that expand under immunotherapy at single-cell level; for example, one subclone is more proliferative, and another is more stem-cell-like. In summary, this study provides an overall picture of the polyclonal competition and changes in the immune microenvironment that are related to resistance to immunotherapy in patients with malignancies.

Indexed as

Carcinoma, Transitional CellImmunotherapyTumor MicroenvironmentUrinary Bladder NeoplasmsDrug Resistance, NeoplasmFemaleHumansImmune Checkpoint InhibitorsMaleMutationNeoplasm MetastasisProgrammed Cell Death 1 ReceptorTranscriptomeImmune Checkpoint InhibitorsPDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID40866351
PMCPMC12391455

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.