Evidence map›Paper›PMID 42898377›Full record

ArticleFrontiers in immunology2026

Comparative profiling of MAIT cells across gastrointestinal cancers identifies conserved NK receptor dysregulation and HCC-specific defects in cytotoxicity and XBP1s signaling.

Vanessa Proß, Annkathrin Helena Ruhm, Linda Marie Laura Thole, Laura Tóth, Gishnu Harikumar Parvathy, Pia Jäger, Christina Götz, Georg Damm, Daniel Seehofer, Christian Bayerl and 14 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
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Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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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

24 authors.

Vanessa ProßDepartment of General and Visceral Surgery, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Annkathrin Helena RuhmDepartment of General and Visceral Surgery, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Linda Marie Laura TholeDepartment of General and Visceral Surgery, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Laura TóthDepartment of General and Visceral Surgery, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Gishnu Harikumar ParvathyDepartment of General and Visceral Surgery, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Pia JägerDepartment of General and Visceral Surgery, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Christina GötzDepartment of Hepatobiliary Surgery and Visceral Transplantation, Clinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, Leipzig, Germany.
Georg DammDepartment of Hepatobiliary Surgery and Visceral Transplantation, Clinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, Leipzig, Germany.
Daniel SeehoferDepartment of Hepatobiliary Surgery and Visceral Transplantation, Clinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, Leipzig, Germany.
Christian BayerlDepartment of Radiology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Hermann HerbstDepartment of Pathology, Vivantes Klinikum Neukölln, Berlin, Germany.
Alexander MackeDepartment of Visceral Surgery, Vivantes Klinikum Neukölln, Berlin, Germany.
Verena FreseDepartment of Visceral Surgery, Vivantes Klinikum Neukölln, Berlin, Germany.
Akio SakakiDepartment of Visceral Surgery, Vivantes Klinikum Neukölln, Berlin, Germany.
Marlene Hanisch-HernandezDepartment of Visceral Surgery, Vivantes Klinikum Neukölln, Berlin, Germany.
Friederike RosseckDepartment of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Sascha TreskatschDepartment of Anesthesiology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany.
Frank FriedersdorffDepartment of Urology, Evangelisches Krankenhaus Königin Elisabeth Herzberge, Berlin, Germany.
Christoph TreeseMedical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Severin DaumMedical Department, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Dominik LaueDepartment of Traumatology and Reconstructive Surgery, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Benjamin RufDepartment of Internal Medicine I, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, Germany.
Sören LukassenCenter of Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
Katja KotschDepartment of General and Visceral Surgery, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background & aims: Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes with cytotoxic capacity and emerging roles in tumour immunity. While MAIT cells express a diverse repertoire of natural killer (NK) receptors, the functional significance of these receptors in gastrointestinal (GI) cancers remains poorly understood. Methods: We characterized the NK receptor repertoire and effector function of MAIT cells across five human GI tumour entities: hepatocellular carcinoma (HCC; n = 30), colorectal liver metastases (CRLM; n = 15), colorectal cancer (CRC; n = 17), pancreatic ductal adenocarcinoma (PDAC; n = 17), and gastric cancer (GC; n = 18), and examined the functional phenotype and cytotoxic potential of primary HCC-derived MAIT cells. Results: MAIT cell frequencies varied across tumour entities and anatomical compartments, with significant intratumoral depletion in HCC compared with matched peritumoral tissue. Across all tumour entities, tumour-infiltrating MAIT cells consistently exhibited a pronounced downregulation of the activating NK receptor NKG2D. This reduction was also evident in peripheral blood MAIT cells but notably reversed following tumour resection and correlated with clinical outcomes. Functionally, IL-15-induced cytotoxicity was impaired in HCC-derived MAIT cells independently of receptor expression, suggesting additional mechanisms of dysfunction. Mechanistically, we report the expression of the endoplasmic reticulum stress-responsive transcription factor X-box binding protein 1 XBP1s (spliced form of XBP1) in circulating and tissue-resident MAIT cells. XBP1s expression was induced by IL-15 and ER stress but was attenuated in tumour-derived compared with peritumoral MAIT cells, indicating defective ER stress signalling. Conclusions: Together, these findings define a distinct dysfunctional state of tumour-resident MAIT cells in HCC, characterized by defective ER stress responses, and identify impaired NK receptor expression across GI cancers that may contribute to impaired antitumour immunity.

Indexed as

Carcinoma, HepatocellularCytotoxicity, ImmunologicGastrointestinal NeoplasmsMucosal-Associated Invariant T CellsReceptors, Natural Killer CellX-Box Binding Protein 1FemaleHumansKiller Cells, NaturalLiver NeoplasmsLymphocytes, Tumor-InfiltratingMaleNK Cell Lectin-Like Receptor Subfamily KSignal TransductionKLRK1 protein, humanNK Cell Lectin-Like Receptor Subfamily KReceptors, Natural Killer CellX-Box Binding Protein 1XBP1 protein, humancytotoxicityHCCmucosa-associated invariant T cellsnatural killer cell receptorsNKG2DXBP1s

Identifiers

PMID42898377
PMCPMC13677909

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