Hung Y.-P.YU-YUN SHAOLee J.-M.CHIUN HSUCHIH-HUNG HSUYang M.-H.Chao Y.2021-08-032021-08-0320211726-4901https://www.scopus.com/inward/record.uri?eid=2-s2.0-85102018356&doi=10.1097%2fJCMA.0000000000000477&partnerID=40&md5=6fe22f8901d883a050459610f00a3d2dhttps://scholars.lib.ntu.edu.tw/handle/123456789/575952Background: Remarkable progress has been made in immunotherapy, specifically antibodies for programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1), for treating advanced cancers. In this study, we explored whether circulating immune cells can be used as biomarkers of the efficacy of such therapy. Methods: We enrolled patients who received nivolumab, an anti-PD-1 antibody, for advanced hepatocellular carcinoma (HCC) in clinical trials and who consented to the collection of their peripheral blood. Using flow cytometry, we analyzed lymphocyte subclasses and the PD-1 or PD-L1 positivity of immune cells. These results were compared between patients with disease control (complete response, partial response, or stable disease) and those with disease progression. Results: This study included 16 patients. The objective response rate was 19%, and the disease control rate was 75%. The hemogram results and the percentage of total αβ T cells or CD4 T cells did not significantly change after nivolumab treatment; moreover, they were not associated with treatment outcomes. The number of CD8 T cells significantly increased after 4 weeks (p=0.016); however, this change was not associated with treatment outcomes. Patients with disease control exhibited peripheral B cells with significantly lower pretreatment PD-1 positivity than did patients with disease progression (p=0.042). Patients with disease progression were more likely to exhibit monocytes with increased PD-L1 positivity after 28 (p=0.020) or 42 (p=0.008) days of treatment. Conclusion: The low pretreatment PD-1 positivity of peripheral B cells and the constant posttreatment PD-L1 positivity of monocytes were associated with disease control after nivolumab treatment for advanced HCC. ? 2020, the Chinese Medical Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)[SDGs]SDG3antineoplastic agent; nivolumab; programmed death 1 ligand 1; programmed death 1 receptor; tumor marker; biological marker; nivolumab; ablation therapy; adult; advanced cancer; aged; alpha beta T lymphocyte; Article; B lymphocyte; blood; cancer control; cancer immunotherapy; CD4+ CD25+ T lymphocyte; CD4+ T lymphocyte; CD8+ T lymphocyte; chemoembolization; clinical article; comparative study; controlled study; correlation coefficient; data analysis software; disease exacerbation; drug efficacy; exploratory research; female; flow cytometry; human; human cell; immunocompetent cell; liver cell carcinoma; liver resection; local therapy; male; monocyte; observational study; percutaneous ethanol injection; peripheral blood mononuclear cell; phase 1 clinical trial (topic); radiofrequency ablation; regulatory T lymphocyte; T lymphocyte; T lymphocyte subpopulation; therapy effect; treatment outcome; treatment response; trend study; tumor ablation; blood; immunotherapy; liver cell carcinoma; liver tumor; middle aged; pathology; Biomarkers; Carcinoma, Hepatocellular; Female; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Liver Neoplasms; Male; Middle Aged; Nivolumab; Treatment Outcomejournal article10.1097/JCMA.0000000000000477334331322-s2.0-85102018356