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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.
- Source :
-
Nature communications [Nat Commun] 2023 Nov 29; Vol. 14 (1), pp. 7825. Date of Electronic Publication: 2023 Nov 29. - Publication Year :
- 2023
-
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 <superscript>+</superscript> CXCL10 <superscript>+</superscript> macrophages and, based on cell-cell interaction analysis, express high levels of CXCL9/10/11 and are predicted to attract peripheral CXCR3 <superscript>+</superscript> CD8 <superscript>+</superscript> effector-memory T cells (CD8 T <subscript>EM</subscript> ) into the tumour. Based on T cell receptor sharing and pseudotime trajectory analysis, we propose that CD8 T <subscript>EM</subscript> preferentially differentiate into clonally-expanded PD1 <superscript>- </superscript> CD45RA <superscript>+</superscript> effector-memory CD8 <superscript>+</superscript> T cells (CD8 T <subscript>EMRA</subscript> ) with pronounced cytotoxicity. In contrast, in non-responders, CD8 T <subscript>EM</subscript> remain frozen in their effector-memory state. Finally, in responders, CD8 T <subscript>EMRA</subscript> 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.<br /> (© 2023. The Author(s).)
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 38030622
- Full Text :
- https://doi.org/10.1038/s41467-023-43381-1