Baseline circulating and tumor γδ T cells and early circulating CD8⁺PD1⁺ expansion predict response to Atezolizumab-bevacizumab in HCC.

We aimed to identify circulating and tumor immune features predictive of oncological outcomes under Atezolizumab-Bevacizumab (AtezoBev) therapy for hepatocellular carcinoma (HCC). We conducted a prospective study in 31 patients treated with first-line AtezoBev, integrating sequential PBMC immunophenotyping, cytokine profiling and whole-blood RNA sequencing. Tumor RNA-sequencing data from clinical trial (GO30140/IMbrave150, 209 AtezoBev and 58 sorafenib-treated patients), together with 163 MSI-H colorectal cancer (CRC) treated by immunotherapy were used to assess the predictive value of immune signatures. Based on PBMC analysis at baseline (87% of male, age 65 years and 65% of BCLC-C), high baseline circulating γδ T-cells was associated with disease control (p=0.006) and longer progression free survival (PFS) (p=0.02).

In tumor RNA-seq, a high intratumoral γδ T signature was also associated with higher response (p