Systemic immune profiling uncovers divergent mechanisms and predictive biomarkers of response to combination immunotherapies in hepatocellular carcinoma - PubMed
5 hours ago
- #hepatocellular carcinoma
- #biomarkers
- #immunotherapy
- Systemic immune profiling in advanced hepatocellular carcinoma (HCC) patients reveals distinct immune mechanisms for two combination immunotherapies: atezolizumab plus bevacizumab (Atez/Bev) and durvalumab plus tremelimumab (Dur/Tre).
- Atez/Bev responders show reprogramming of CD14+ monocytes towards antigen-presenting functions and enhanced cytotoxicity in PRKCH+ NK cells via monocyte-NK interactions.
- Dur/Tre responders exhibit CD14+ monocyte programs enriched in inflammatory antigen presentation and reprogramming of CD8+ central memory T cells into an effector-ready state.
- T cell receptor (TCR) analysis indicates regimen-specific differences: Atez/Bev leads to clonotype expansion regardless of response, while Dur/Tre responders show both clonotype expansion and higher pretreatment CD8+ T cell diversity.
- Pretreatment biomarkers predict response: naïve CD4+ T cells and PRKCH+ NK cells for Atez/Bev, and conventional dendritic cells for Dur/Tre.
- The study highlights divergent systemic immune pathways, suggesting tailored immunotherapy approaches based on specific regimen mechanisms.