Evidence map›Paper›PMID 38527308›Full record

ArticleCancer science2024

Molecular subtypes of lung adenocarcinoma present distinct immune tumor microenvironments.

Hironori Fukuda, Kosuke Arai, Hideaki Mizuno, Yukari Nishito, Noriko Motoi, Yasuhito Arai, Nobuyoshi Hiraoka, Tatsuhiro Shibata, Yukiko Sonobe, Yoko Kayukawa and 31 more

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 20% of its field
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 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
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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

41 authors at 11 institutions in 3 countries.

Hironori FukudaDepartment of Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.
Kosuke AraiDepartment of Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.ORCID https://orcid.org/0000-0003-1106-8329
Hideaki MizunoChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Yukari NishitoChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Noriko MotoiDepartment of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
Yasuhito AraiDivision of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
Nobuyoshi HiraokaDepartment of Analytical Pathology, National Cancer Center Research Institute, Tokyo, Japan.ORCID https://orcid.org/0000-0003-4215-4385
Tatsuhiro ShibataDivision of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
Yukiko SonobeChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Yoko KayukawaChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Eri HashimotoChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Mina TakahashiChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Etsuko FujiiChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Toru MaruyamaChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Kenta KuwabaraChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Takashi NishizawaChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Yukihiro MizoguchiDepartment of Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.
Yukihiro YoshidaDepartment of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
Shun-Ichi WatanabeDepartment of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
Makiko YamashitaAdvanced Medical Development Center, Cancer Research Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Shigehisa KitanoAdvanced Medical Development Center, Cancer Research Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.ORCID https://orcid.org/0000-0002-4041-8298
Hiromi SakamotoDepartment of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan.
Yuki NagataMedical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Japan.
Risa MitsumoriMedical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Japan.
Kouichi OzakiMedical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Japan.
Shumpei NiidaMedical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Japan.
Yae KanaiDepartment of Pathology, School of Medicine, Keio University, Tokyo, Japan.
Akiyoshi HirayamaInstitute for Advanced Biosciences, Keio University, Yamagata, Japan.
Tomoyoshi SogaInstitute for Advanced Biosciences, Keio University, Yamagata, Japan.
Keisuke TsukadaChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Nami YabukiChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Mei ShimadaChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Takehisa KitazawaChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Osamu NatoriChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Noriaki SawadaChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Atsuhiko KatoChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Teruhiko YoshidaDepartment of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan.
Kazuki YasudaDepartment of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Atsushi OchiaiExploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.ORCID https://orcid.org/0000-0001-6857-4009
Hiroyuki TsunodaChugai Life Science Park Yokohama, Chugai Pharmaceutical Co. Ltd, Yokohama, Japan.
Kazunori AokiDepartment of Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.ORCID https://orcid.org/0000-0002-1292-3764
Chugai Pharma (United States) · USKeio University · JPNational Center for Geriatrics and Gerontology · JPTokyo National Hospital · JPJapanese Foundation For Cancer Research · JPTokyo Medical and Dental University · JPChiba Cancer Center · JPNational Cancer Center Hospital East · JPNational Cancer Research Institute · GBNational Center for Global Health and Medicine · JPTokyo Women's Medical University · JP

Funding

Japan Agency for Medical Research and Development 21ck010640h0002Japan Agency for Medical Research and Development 21ck0106532h0002Japan Agency for Medical Research and Development JP19ak0101043h0105AJapan Agency for Medical Research and Development JP19ak0101044h0104Japan Society for the Promotion of Science 18K07036Japan Society for the Promotion of Science 21K06900Japan Society for the Promotion of Science 21K07951
6 · The paper itself

Abstract

Overcoming resistance to immune checkpoint inhibitors is an important issue in patients with non-small-cell lung cancer (NSCLC). Transcriptome analysis shows that adenocarcinoma can be divided into three molecular subtypes: terminal respiratory unit (TRU), proximal proliferative (PP), and proximal inflammatory (PI), and squamous cell carcinoma (LUSQ) into four. However, the immunological characteristics of these subtypes are not fully understood. In this study, we investigated the immune landscape of NSCLC tissues in molecular subtypes using a multi-omics dataset, including tumor-infiltrating leukocytes (TILs) analyzed using flow cytometry, RNA sequences, whole exome sequences, metabolomic analysis, and clinicopathologic findings. In the PI subtype, the number of TILs increased and the immune response in the tumor microenvironment (TME) was activated, as indicated by high levels of tertiary lymphoid structures, and high cytotoxic marker levels. Patient prognosis was worse in the PP subtype than in other adenocarcinoma subtypes. Glucose transporter 1 (GLUT1) expression levels were upregulated and lactate accumulated in the TME of the PP subtype. This could lead to the formation of an immunosuppressive TME, including the inactivation of antigen-presenting cells. The TRU subtype had low biological malignancy and "cold" tumor-immune phenotypes. Squamous cell carcinoma (LUSQ) did not show distinct immunological characteristics in its respective subtypes. Elucidation of the immune characteristics of molecular subtypes could lead to the development of personalized immune therapy for lung cancer. Immune checkpoint inhibitors could be an effective treatment for the PI subtype. Glycolysis is a potential target for converting an immunosuppressive TME into an antitumorigenic TME in the PP subtype.

Indexed as

Adenocarcinoma of LungGlucose Transporter Type 1Lung NeoplasmsLymphocytes, Tumor-InfiltratingTumor MicroenvironmentAgedCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMiddle AgedPrognosisGlucose Transporter Type 1SLC2A1 protein, humanimmunotherapylung cancermolecular subtypetumor‐infiltrating lymphocytetumor microenvironment

Identifiers

PMID38527308
PMCPMC11145114
OpenAlexW4393139489

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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.