Evidence map›Paper›PMID 41364047›Full record

ArticleCytotherapy2026

Expanded adaptive NKG2C+ NK cells exhibit potent ADCC and functional responses against HBV-infected hepatoma cell lines.

Jonida Kokiçi, Helena Arellano-Ballestero, Benjamin Hammond, Anucha Preechanukul, Noshin Hussain, Kelly da Costa, Jessica Davies, Sadiyah Mukhtar, Thomas Fernandez, Sabine Kinloch and 10 more

Abstract read
In one paragraph

Article in Cytotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Jonida KokiçiDivision of Infection and Immunity, UCL, London, UK.
Helena Arellano-BallesteroCancer Institute, UCL, London, UK.
Benjamin HammondINmune Bio International, Royal Free Hospital, London, UK.
Anucha PreechanukulDivision of Infection and Immunity, UCL, London, UK.
Noshin HussainDivision of Infection and Immunity, UCL, London, UK.
Kelly da CostaDivision of Infection and Immunity, UCL, London, UK.
Jessica DaviesDivision of Infection and Immunity, UCL, London, UK.
Sadiyah MukhtarMortimer Market Centre, Department of HIV, CNWL NHS Trust, London, UK.
Thomas FernandezRoyal Free London NHS Foundation Trust, London, UK.
Sabine KinlochRoyal Free London NHS Foundation Trust, London, UK.
Fiona M BurnsRoyal Free London NHS Foundation Trust, London, UK; Institute for Global Health, UCL, London, UK.
Patrick KennedyBarts Liver Centre, Centre for Immunobiology, Barts and the London School of Medicine & Dentistry, QMUL, UK.
Douglas MacDonaldRoyal Free London NHS Foundation Trust, London, UK.
Mala K MainiDivision of Infection and Immunity, UCL, London, UK.
Upkar S GillBarts Liver Centre, Centre for Immunobiology, Barts and the London School of Medicine & Dentistry, QMUL, UK.
Alan Xiaodong ZhuangDivision of Infection and Immunity, UCL, London, UK.
Mark W LowdellDivision of Infection and Immunity, UCL, London, UK.
Karl-Johan MalmbergCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Ebba SohlbergCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Dimitra PeppaDivision of Infection and Immunity, UCL, London, UK; Mortimer Market Centre, Department of HIV, CNWL NHS Trust, London, UK; Royal Free London NHS Foundation Trust, London, UK. Electronic address: d.peppa@ucl.ac.uk.

Funding

Exploiting Natural Killer cells in HIV/HBV co-infection to achieve eradicationR01AI155182 · NIAID · UNIVERSITY OF OXFORD · PI PEPPA, DIMITRA · 2020 to 2024
$1.9M
NIAID NIH HHS R01 AI155182
6 · The paper itself

Abstract

backgroundHepatitis B virus (HBV) infection remains a significant global health challenge, leading to chronic liver disease and hepatocellular carcinoma (HCC). Natural killer (NK) cells play an important role in the clearance of HBV-infected cells, but their efficacy is often compromised during chronic infection. Adaptive NK cells, characterized by NKG2C expression and enhanced functional responses, represent a promising therapeutic avenue for enhancing anti-HBV immunity and responses to HBV-driven cancers.

methodsWe applied an established protocol, involving K562-HLA-E expressing feeder cells and cytokines (IL-2), for the expansion of adaptive NK cells from cryopreserved T- and B cell depleted peripheral blood mononuclear cells (PBMCs) derived from donors with chronic HBV infection alone or with Human Immunodeficiency Virus (HIV) co-infection. We evaluated the adaptive profile of expanded NK cells, their antibody-dependent cellular cytotoxicity (ADCC) capacity and functional responses against hepatoma cell lines in the presence or absence of HBV infection.

resultsExpanded NK cells achieved >97% purity, with the NKG2C positive population exhibiting a mean 100-fold expansion. These cells demonstrated a predominantly adaptive phenotype with high surface expression of NKG2C and cytotoxic potential (Granzyme B). They maintained high levels of CD16 surface expression and upregulated CD2, essential for ADCC. Functionally, expanded adaptive NK cells showed enhanced ADCC capacity and functional responses to K562 targets, naive, HBV integrant-expressing, and de novo infected hepatoma cell lines. TGF-β preconditioning induced tissue-resident features (CD103, CD49a) in expanded adaptive NK cells, while preserving their adaptive phenotype and functionality, enhancing their potential for liver targeted immunotherapy. Further, expanded adaptive NK cells demonstrated minimal reactivity against autologous activated T cells, suggesting limited off-target effects.

conclusionsOur study demonstrates the first successful expansion of adaptive NK cells with robust functional responses from donors with chronic viral infection. This approach creates opportunities for NK cell-based therapies alone or in combination with monoclonal antibodies contributing to HBV functional cure strategies and the treatment of HBV-driven cancers.

Indexed as

Antibody-Dependent Cell CytotoxicityCarcinoma, HepatocellularHepatitis BHepatitis B virusKiller Cells, NaturalLiver NeoplasmsNK Cell Lectin-Like Receptor Subfamily CCell Line, TumorHepatitis B, ChronicHumansK562 CellsKLRC2 protein, humanNK Cell Lectin-Like Receptor Subfamily Cadaptive immunityantiviral therapyhepatitis B virusimmunotherapynatural killer cells

Identifiers

PMID41364047
PMCPMC13274919

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.