Circulating CD8 Lymphocytes Predict Response to Atezolizumab-Bevacizumab in Hepatocellular Carcinoma.

Due to lack of biomarkers predictive of response to atezolizumab-bevacizumab, the standard of care for advanced HCC, we analyzed baseline and early on treatment variation in peripheral lymphocytes of 37 prospective patients treated by atezolizumab-bevacizumab and in 15 prospective patients treated by sorafenib or lenvatinib (TKIs). RNAseq analysis followed by RT-PCR validation on patients-derived PBMC was also performed. At first imaging re-evaluation 13 patients receiving atezolizumab-bevacizumab, showed objective response, 17 stable diseases, while 7 were non-responder. Baseline CD8+ and CD8+PD-L1+ peripheral lymphocytes were lower in responders versus non-responders (T-test, p = 0.012 and p = 0.004 respectively). At 3-weeks, 28 of 30 responders displayed a rise of CD8+PD1+ lymphocytes with a positive mean fold change of 4.35 (±5.6 SD) while 6 of 7 non-responders displayed a negative fold change of 0.89 (±0.84 SD). These changes were not observed in patients treated by TKIs. TRIM56, TRIM16, TRIM64 and Ki67 mRNAs were validated as up-regulated in responders versus non responders after 3 weeks from treatments start, providing a possible evidence of immune activation. Baseline CD8+ and CD8+PD-L1+ peripheral lymphocytes and early changes in CD8+PD1+ lymphocytes predict response to atezolizumab-bevacizumab providing non-invasive markers to complement clinical practice in the very early phases of treatment of HCC patients. This article is protected by copyright. All rights reserved.