{"entity": "publication", "iuid": "25a623e998354a7488511533f4ed529d", "timestamp": "2026-09-24T14:47:23.456Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/25a623e998354a7488511533f4ed529d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/25a623e998354a7488511533f4ed529d"}}, "title": "Human MAIT cells endowed with HBV specificity are cytotoxic and migrate towards HBV-HCC while retaining antimicrobial functions.", "authors": [{"family": "Healy", "given": "Katie", "initials": "K"}, {"family": "Pavesi", "given": "Andrea", "initials": "A"}, {"family": "Parrot", "given": "Tiphaine", "initials": "T"}, {"family": "Sobkowiak", "given": "Micha\u0142 J", "initials": "MJ"}, {"family": "Reinsbach", "given": "Susanne E", "initials": "SE"}, {"family": "Davanian", "given": "Haleh", "initials": "H"}, {"family": "Tan", "given": "Anthony T", "initials": "AT"}, {"family": "Aleman", "given": "Soo", "initials": "S"}, {"family": "Sandberg", "given": "Johan K", "initials": "JK"}, {"family": "Bertoletti", "given": "Antonio", "initials": "A"}, {"family": "S\u00e4llberg Chen", "given": "Margaret", "initials": "M"}], "type": "journal article", "published": "2021-08-00", "journal": {"title": "JHEP Rep", "issn": "2589-5559", "volume": "3", "issue": "4", "pages": "100318", "issn-l": null}, "abstract": "Virus-specific T cell dysfunction is a common feature of HBV-related hepatocellular carcinoma (HBV-HCC). Conventional T (ConT) cells can be redirected towards viral antigens in HBV-HCC when they express an HBV-specific receptor; however, their efficacy can be impaired by liver-specific physical and metabolic features. Mucosal-associated invariant T (MAIT) cells are the most abundant innate-like T cells in the liver and can elicit potent intrahepatic effector functions. Here, we engineered ConT and MAIT cells to kill HBV expressing hepatoma cells and compared their functional properties.\n\nDonor-matched ConT and MAIT cells were engineered to express an HBV-specific T cell receptor (TCR). Cytotoxicity and hepatocyte homing potential were investigated using flow cytometry, real-time killing assays, and confocal microscopy in 2D and 3D HBV-HCC cell models. Major histocompatibility complex (MHC) class I-related molecule (MR1)-dependent and MR1-independent activation was evaluated in an Escherichia coli THP-1 cell model and by IL-12/IL-18 stimulation, respectively.\n\nHBV TCR-MAIT cells demonstrated polyfunctional properties (CD107a, interferon [IFN] \u03b3, tumour necrosis factor [TNF], and IL-17A) with strong HBV target sensitivity and liver-homing chemokine receptor expression when compared with HBV TCR-ConT cells. TCR-mediated lysis of hepatoma cells was comparable between the cell types and augmented in the presence of inflammation. Coculturing with HBV+ target cells in a 3D microdevice mimicking aspects of the liver microenvironment demonstrated that TCR-MAIT cells migrate readily towards hepatoma targets. Expression of an ectopic TCR did not affect the ability of the MAIT cells to be activated via MR1-presented bacterial antigens or IL-12/IL-18 stimulation.\n\nHBV TCR-MAIT cells demonstrate anti-HBV functions without losing their endogenous antimicrobial mechanisms or hepatotropic features. Our results support future exploitations of MAIT cells for liver-directed immunotherapies.\n\nChronic HBV infection is a leading cause of liver cancer. T cell receptor (TCR)-engineered T cells are patients' immune cells that have been modified to recognise virus-infected and/or cancer cells. Herein, we evaluated whether mucosal-associated invariant T cells, a large population of unconventional T cells in the liver, could recognise and kill HBV infected hepatocytes when engineered with an HBV-specific TCR. We show that their effector functions may exceed those of conventional T cells currently used in the clinic, including antimicrobial properties and chemokine receptor profiles better suited for targeting liver tumours.", "doi": "10.1016/j.jhepr.2021.100318", "pmid": "34377970", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8327138"}, {"db": "pii", "key": "S2589-5559(21)00094-X"}], "notes": [], "created": "2026-09-23T11:54:55.518Z", "modified": "2026-09-23T11:54:55.543Z"}