Spatial single-cell profiling and neighbourhood analysis reveal the determinants of immune architecture connected to checkpoint inhibitor therapy outcome in hepatocellular carcinoma
Bioinformatic analysis identified 23 major immune, stroma, parenchymal and tumour cell types in the HCC TME. Unsupervised neighbourhood detection based on the spatial interaction of immune cells identified three immune architectures with differing involvement of immune cells and immune checkpoints dominated by either CD8 T-cells, myeloid immune cells or B- and CD4 T-cells. We used these to define three major spatial HCC immunotypes that reflect a higher level of intratumour immune cell organisation: depleted, compartmentalised and enriched. Progression-free survival under ICI therapy differed significantly between the spatial immune types with improved survival of enriched patients. In patients with intratumour heterogeneity, the presence of one enriched area governed long-term survival.
Authors
- David James Pinato (ORCID: https://orcid.org/0000-0002-3529-0103)
- Michael Schultheiß (ORCID: https://orcid.org/0000-0001-8000-1721)
- Melanie Boerries (ORCID: https://orcid.org/0000-0002-3670-0602)
- Antonio D’Alessio (ORCID: https://orcid.org/0000-0002-9164-3671)
- Yuan Suo
- Ira Godbole
- Lara Wischer
- Bertram Bengsch (ORCID: https://orcid.org/0000-0003-2552-740X)
- Henrike Salié (ORCID: https://orcid.org/0000-0002-2993-3782)
- Andreas Blaumeiser
- Thomas Longerich (ORCID: https://orcid.org/0000-0001-8888-1030)
- Patricia Otto-Mora
- Claudia Angela Maria Fulgenzi (ORCID: https://orcid.org/0000-0002-5654-9225)
- Maike Hofmann (ORCID: https://orcid.org/0000-0001-8410-8833)
- Robert Thimme (ORCID: https://orcid.org/0000-0003-1417-4135)
- Olaf Neumann (ORCID: https://orcid.org/0000-0003-2684-9187)
- Natascha Roehlen (ORCID: https://orcid.org/0000-0002-6653-8765)
- Jürgen Beck (ORCID: https://orcid.org/0000-0001-8794-9320)
- Peter Schirmacher
- Albrecht Stenzinger
Institutions
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- University of Freiburg (DE)
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- University Medical Center Freiburg (DE)
- University Hospital Heidelberg (DE)
- Imperial College London (GB)
Publication Details
- Journal
- Gut
- Published
- 2024-09-30
- DOI
- https://doi.org/10.1136/gutjnl-2024-332837
- Citations
- 43
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 12.15
Funders
- Wellcome Trust
- Bundesministerium für Bildung und Forschung
- European Association for the Study of the Liver
- Cancer Treatment and Research Trust
- NIHR Imperial Biomedical Research Centre