Potential of circulating immune cells as biomarkers of nivolumab treatment efficacy for advanced hepatocellular carcinoma

Yi Ping Hung, Yu Yun Shao, Jan Mou Lee, Chiun Hsu, Chih Hung Hsu, Muh Hwa Yang*, Yee Chao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background: 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.

Original languageEnglish
Pages (from-to)144-150
Number of pages7
JournalJournal of the Chinese Medical Association
Issue number2
StatePublished - Feb 2021


  • Flow cytometry
  • Hepatocellular carcinoma
  • Immunotherapy
  • Nivolumab
  • Predictive markers


Dive into the research topics of 'Potential of circulating immune cells as biomarkers of nivolumab treatment efficacy for advanced hepatocellular carcinoma'. Together they form a unique fingerprint.

Cite this