Evidence map›Paper›PMID 42538270›Full record

ArticleEBioMedicine2026

d-serine as a metabolic immune checkpoint in the tumour microenvironment.

Kai Tsugaru, Shohei Suzuki, Kentaro Miyamoto, Kazuhiro Murakami, Akihiko Chida, Chihiro Kato, Naoto Fukasawa, Arina Shigehara, Mai Hasegawa, Yusuke Yoshimatsu and 18 more

Abstract read
In one paragraph

Article in EBioMedicine, 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

28 authors.

Kai TsugaruDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Shohei SuzukiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Kentaro MiyamotoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan; Miyarisan Pharmaceutical Co., Ltd., Research Laboratory, Tokyo, 114-0016, Japan.
Kazuhiro MurakamiDivision of Epithelial Stem Cell Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Akihiko ChidaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Chihiro KatoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Naoto FukasawaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Arina ShigeharaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Mai HasegawaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Yusuke YoshimatsuDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Jumpei SasabeLaboratory of Electron Microscopy and Chiral Medical Biology, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Masashi MitaKagami Inc., Osaka, Japan.
Nick BarkerInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A∗Star), 138673, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore.
Yosuke HaradaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Yasutaka SukawaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Toshiaki TerataniDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Nobuhiro NakamotoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Hirofumi KawakuboDepartment of Surgery, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Kaoru TakabayashiCenter for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Motohiko KatoCenter for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Naohisa YahagiDivision of Research and Development for Minimally Invasive Treatment Cancer Center, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Taisuke KondoDivision of Tumour Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Eri AraiDepartment of Pathology, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Yuko KitagawaDepartment of Surgery, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Kenro HirataDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Yasuo HamamotoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan; Department of Medical Oncology, Institute of Science Tokyo, Bunkyo-ku, Tokyo, 113-8519, Japan.
Takanori KanaiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 160-8582, Japan. Electronic address: takagast@keio.jp.
Tomohisa SujinoDepartment of Multidimensional Analysis of Gastrointestinal Biology, The Sakaguchi Laboratory, Keio University School of Medicine, Tokyo, 160-8582, Japan. Electronic address: tsujino1224@keio.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundd-amino acids (D-AAs), the enantiomers of proteinogenic l-amino acids, are detectable in mammals, yet their biological roles in cancer immunity remain largely unexplored. Whether specific D-AAs modulate tumour progression or influence responsiveness to immunotherapy in gastrointestinal cancer is unknown. We aimed to determine how D-AAs, particularly d-serine (D-ser), shape the tumour immune microenvironment and affect clinical outcomes in gastrointestinal cancers.

methodsMechanistic studies were conducted using murine MC38 tumours and orthotopic gastric cancer (GC) organoid allografts with or without D-AAs supplementation. Immune landscape alterations were assessed using single-cell RNA sequencing of tumour-infiltrating immune cells, flow cytometry, ex vivo macrophage-T cell co-culture assays, and microbiome manipulation experiments. D-AAs concentrations in plasma, urine, and stool were quantified in healthy controls (HCs; n = 87) and patients with GC across three cohorts (Cohort 1, n = 14; Cohort 2, n = 108; Cohort 3, n = 28). Associations between plasma D-ser levels, disease stage, immune cell infiltration, and clinical outcomes following anti-PD-1 antibody therapy were analysed.

findingsD-ser promoted tumour progression by suppressing CD8

interpretationThis study identifies D-ser as a previously unrecognised immunosuppressive metabolite that promotes tumour immune evasion by increased macrophages and reduced CD8

fundingThis work was supported by The Japan Science and Technology Agency (JST) Fusion Oriented Research for Disruptive Science and Technology (FOREST)[JPMJFR210P], Grants-in-Aid from the Japanese Society for the Promotion of Science (JSPS) (25K10430, 21K18272, 23H02899, 23K27590, 25K22627), KGRI challenge grant, Sakaguchi Memorial Foundation, Japan Agency for Medical Research and Development (CREST 21gm1510002h0001), and Miyarisan Pharmaceutical Grant.

Indexed as

SerineStomach NeoplasmsTumor MicroenvironmentAnimalsCD8-Positive T-LymphocytesCell Line, TumorDisease Models, AnimalFemaleHumansLymphocytes, Tumor-InfiltratingMacrophagesMaleMiceSerineCD8(+) T cellsd-serineGastric cancerMacrophagesMetabolite

Identifiers

PMID42538270
PMCPMC13476903

What Socratic holds

Textmetadata
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.