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

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, Baki Topal, Orian Bricard, Junbin Qian, Eric Van Cutsem, Chris Verslype, Diether Lambrechts () and Jeroen Dekervel ()
Additional contact information
Sarah Cappuyns: University Hospitals Leuven
Gino Philips: Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
Vincent Vandecaveye: University Hospitals Leuven
Bram Boeckx: Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
Rogier Schepers: Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
Thomas Van Brussel: Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
Ingrid Arijs: Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
Aurelie Mechels: Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
Ayse Bassez: Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
Francesca Lodi: Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
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
Junbin Qian: Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
Eric Van Cutsem: University Hospitals Leuven
Chris Verslype: University Hospitals Leuven
Diether Lambrechts: Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
Jeroen Dekervel: University Hospitals Leuven

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43381-1

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