Z Gastroenterol 2025; 63(01): e53
DOI: 10.1055/s-0044-1801156
Abstracts │ GASL
Poster Visit Session IV
TUMORS 15/02/2025, 08.30am – 09.10am

Characterization of T cell subsets and dynamic remodeling following immune checkpoint inhibition in hepatocellular carcinoma

Emilia Schlaak
1   Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
,
Antonio D'Alessio
2   Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Patricia Otto-Mora
1   Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
,
Jürgen Beck
1   Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
,
Günter Päth
1   Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
,
Claudia A.M. Fulgenzi
2   Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Pai Madhava
3   Division of Surgery, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Robert D. Goldin
4   Centre for Pathology, Imperial College London, Charing Cross Hospital, Fulham Palace Road, London, UK.
,
Bernhard Scheiner
2   Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
James A. Korolewicz
2   Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Duncan Spalding
3   Division of Surgery, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Caroline Ward
2   Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Georgios Nteliopoulos
2   Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Heng Cai
2   Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Chloe John
2   Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Vincet Yip
5   Barts and The London HPB Centre, The Royal London Hospital, Barts Health NHS Trust, London, UK.
,
Sarah Slater
6   Department of Medical Oncology, Barts Health NHS Trust, London, UK.
,
Ayse U. Akarca
7   Department of Histopathology, University College Hospitals London, London, UK.
,
Mikael Sodergren
3   Division of Surgery, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Paul Tait
8   Department of Radiology, Imperial College NHS Trust, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Nagy Habib
3   Division of Surgery, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Robert Thomas
8   Department of Radiology, Imperial College NHS Trust, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Alessio Cortellini
2   Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Teresa Marafioti
7   Department of Histopathology, University College Hospitals London, London, UK.
,
Julian R. Marchesi
9   Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
,
Robert Thimme
1   Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
,
Rohini Sharma
2   Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
David J. Pinato
2   Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
,
Bertram Bengsch
1   Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
› Author Affiliations
› Further Information
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Immune-checkpoint inhibitors (ICIs) have recently shown promising results in advanced hepatocellular carcinoma (HCC) by targeting molecules like PD-1 and CTLA-4 to enhance anti-tumor immunity. In the prospective phase 1b HCC-PRIME study, safety and efficacy of ipilimumab and nivolumab combination prior to liver resection were analyzed. Here we investigate whether neoadjuvant ICI induces changes in the peripheral immune compartment and if these changes are associated with therapeutic efficacy.

30 patients with radiologically or histologically confirmed HCC were included. Ipilimumab was given once on Day1, and nivolumab on Day1 and Day22, over two 21-day cycles. Blood samples were collected at Cycle1 and 3 weeks post-treatment. Response to therapy was based on radiological criteria (RECISTv1.1 criteria). Peripheral blood mononuclear cells (PBMCs) were analyzed using cytometry by time of flight (CyTOF).

Our study demonstrated remodeling of the peripheral immune landscape during the initial weeks of checkpoint-inhibition therapy, affecting both CD4 and CD8 T-cell compartments. High-dimensional data analysis identified a CD8Tex cluster (PD1+TOX+CD38+TIGIT+GzmK+), which was elevated in responders at baseline and further increased in all patients following therapy. Furthermore, a CD8+PD1+CD103+population that co-expressed CXCR6 and showing a large percentage of nivolumab binding(IgG4+) was enriched post-therapy, suggesting a relationship to tumor resident T-cells responsive to ICI. In the CD4 compartment, regulatory T-cells(CD127+FoxP3+) were expanded, while T follicular helper cells (PD1+CD127+CXCR5+) decreased after treatment.

Our findings provide insight into the dynamic immune remodeling of T-cell subsets following immune checkpoint inhibition in HCC patients, suggesting that monitoring T cell dynamics may serve as a biomarker for therapy efficacy.



Publication History

Article published online:
20 January 2025

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