A simple characterization of dynamic changes in circulating CD8+PD1+ lymphocytes early predicts response to atezolizumab-bevacizumab in hepatocellular carcinoma. (March 2023)

• Record Type: Journal Article
• Authors: Giovannini, C.; Suzzi, F.; Tovoli, F.; Bruccoleri, M.; Marseglia, M.; Alimenti, E.; Fornari, F.; Iavarone, M.; Piscaglia, F.; Gramantieri, L.
• Is Part Of: Digestive and liver disease. Volume 55(2023)Supplement 1
• Page Start: S13
• Page End: S14
• Publication Date: 2023-03
• Subjects: Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; 616.33005
• DOI: 10.1016/j.dld.2023.01.024
• Languages: English
• ISSNs: 1590-8658

Abstract

Abstract : Atezolizumab+bevacizumab improves survival of patients with advanced Hepatocarcinoma (HCC) in comparison to Sorafenib. No biomarker predicts responders from non-responders to atezolizumab+bevacizumab or patients who benefit from this combination instead of TKIs. To identify early on treatment predictive biomarkers, we investigated whether baseline and early on treatment variation of CD8+, PD1+, PD-L1+, CD8+PD1+, CD8+PDL1+ peripheral lymphocytes might offer a non-invasive, cheap and feasible assay. Methods A prospective cohort of 31 patients treated with atezolizumab+bevacizumab and a control prospective cohort of 15 patients treated with sorafenib or lenvatinib were subjected to repeated blood tests, at baseline and during the course of treatments. At first imaging re-evaluation, 11 patients receiving atezolizumab+bevacizumab showed objective response, 13 stable disease, accounting for the responder group, while 7 patients displayed tumor progression, corresponding to primary non-response. Baseline and early on treatment variation of CD8+, PD1+, PD-L1+, CD8+PD1+, CD8+PDL1+ peripheral lymphocytes were tested by cytofluorimetric analysis and compared in responders and non-responders. Results Baseline CD8+ and CD8+PDL1+ peripheral lymphocytes were lower in responders versus non-responders (mean±SD CD8+: 68±30 vs 95±5; T-test, p<0.0001; mean ±SD CD8+PD-L1+: 77± 9.4 vs 82±4.6; T-test: p=0.004 respectively). Dynamic changes in CD8+PD1+ lymphocytes assessed at 3-weeks, before the second drug infusion, were the most informative test: 22 of 24 responders displayed a rise of CD8+PD1+ peripheral lymphocytes with a positive mean fold change of 4.63 (±5.5 SD). Conversely, 6 of 7 non-responders displayed a negative mean fold change of 0.89 (±0.84 SD) of CD8+PD1+ lymphocytes. These changes were restricted to patients treated with atezolizumab+bevacizumab, while they were not documented in TKI patients, irrespective of the response. Conclusion . Early changes in circulating PD1+CD8+ lymphocytes predict the type of response to atezolizumab+bevacizumab and encourage evaluating this minimally invasive, cheap, easy and repeatable test in a larger cohort of patients to confirm its informativeness in this setting.