In:
Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-11-29)
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 T EM ) into the tumour. Based on T cell receptor sharing and pseudotime trajectory analysis, we propose that CD8 T EM preferentially differentiate into clonally-expanded PD1 - CD45RA + effector-memory CD8 + T cells (CD8 T EMRA ) with pronounced cytotoxicity. In contrast, in non-responders, CD8 T EM remain frozen in their effector-memory state. Finally, in responders, CD8 T EMRA 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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-023-43381-1
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
2553671-0
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