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PD-1- CD45RA+ effector-memory CD8 T cells and CXCL10+ macrophages are associated with response to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma

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  • Sarah Cappuyns

    (University Hospitals Leuven
    Laboratory of Clinical Digestive Oncology, Department of Oncology, KU Leuven
    Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology)

  • Gino Philips

    (Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology)

  • Vincent Vandecaveye

    (University Hospitals Leuven
    Laboratory of Translational MRI, Department of Imaging and Pathology, KU Leuven)

  • Bram Boeckx

    (Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology)

  • Rogier Schepers

    (Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology)

  • Thomas Van Brussel

    (Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology)

  • Ingrid Arijs

    (Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology)

  • Aurelie Mechels

    (Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology)

  • Ayse Bassez

    (Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology)

  • Francesca Lodi

    (Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology)

  • Joris Jaekers

    (University Hospitals Leuven)

  • Halit Topal

    (University Hospitals Leuven)

  • Baki Topal

    (University Hospitals Leuven)

  • Orian Bricard

    (Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology)

  • Junbin Qian

    (Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology
    Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Eric Van Cutsem

    (University Hospitals Leuven
    Laboratory of Clinical Digestive Oncology, Department of Oncology, KU Leuven)

  • Chris Verslype

    (University Hospitals Leuven
    Laboratory of Clinical Digestive Oncology, Department of Oncology, KU Leuven)

  • Diether Lambrechts

    (Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
    VIB Centre for Cancer Biology)

  • Jeroen Dekervel

    (University Hospitals Leuven
    Laboratory of Clinical Digestive Oncology, Department of Oncology, KU Leuven)

Abstract

The combination of atezolizumab plus bevacizumab (atezo/bev) has dramatically changed the treatment landscape of advanced HCC (aHCC), achieving durable responses in some patients. Using single-cell transcriptomics, we characterize the intra-tumoural and peripheral immune context of patients with aHCC treated with atezo/bev. Tumours from patients with durable responses are enriched for PDL1+ CXCL10+ macrophages and, based on cell–cell interaction analysis, express high levels of CXCL9/10/11 and are predicted to attract peripheral CXCR3+ CD8+ effector-memory T cells (CD8 TEM) into the tumour. Based on T cell receptor sharing and pseudotime trajectory analysis, we propose that CD8 TEM preferentially differentiate into clonally-expanded PD1- CD45RA+ effector-memory CD8+ T cells (CD8 TEMRA) with pronounced cytotoxicity. In contrast, in non-responders, CD8 TEM remain frozen in their effector-memory state. Finally, in responders, CD8 TEMRA display a high degree of T cell receptor sharing with blood, consistent with their patrolling activity. These findings may help understand the possible mechanisms underlying response to atezo/bev in aHCC.

Suggested Citation

  • Sarah Cappuyns & Gino Philips & Vincent Vandecaveye & Bram Boeckx & Rogier Schepers & Thomas Van Brussel & Ingrid Arijs & Aurelie Mechels & Ayse Bassez & Francesca Lodi & Joris Jaekers & Halit Topal &, 2023. "PD-1- CD45RA+ effector-memory CD8 T cells and CXCL10+ macrophages are associated with response to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43381-1
    DOI: 10.1038/s41467-023-43381-1
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