The effects of stereotactic body radiotherapy on peripheral natural killer and CD3+CD56+ NKT-like cells in patients with hepatocellular carcinoma

Hepatobiliary Pancreat Dis Int. 2021 Jun;20(3):240-250. doi: 10.1016/j.hbpd.2020.12.015. Epub 2021 Jan 5.

Abstract

Background: Both natural killer (NK) and CD3+CD56+natural killer T (NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy (SBRT) on peripheral NK and NKT-like cells in patients with hepatocellular carcinoma (HCC), and to identify possible surface markers on these cells that correlate with the prognosis.

Methods: Twenty-five HCC patients were prospectively enrolled in our study, and 10 healthy individuals were served as healthy controls. Flow cytometry was used to determine the counts and the percentages of peripheral NK and NKT-like cells, cells with certain receptors, and cells with intracellular interferon-γ and TNF-α secretion at different time points, including time points of prior to SBRT, at post-SBRT, and 3-month and 6-month after treatment. The Kaplan-Meier method with the log-rank test was applied for survival analysis.

Results: The peripheral NKT-like cells was increased at post-SBRT. Meanwhile, elevated levels of inhibitory receptors and reduced levels of activating receptors of NK cells were also observed in NK cells at post-SBRT, but the levels was not significantly different at 3-month and 6-month as compared with the baseline levels. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT were associated with poor progression-free survival. In addition, higher percentage of CD3+CD56+ NKT-like cells was associated with a higher overall survival rate in HCC patients.

Conclusions: SBRT has an apparent effect on both peripheral NK and CD3+CD56+NKT-like cells. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT are correlated with poor patients' PFS. Higher percentage of CD3+CD56+ NKT-like cells is associated with higher OS in HCC patients.

Keywords: Hepatocellular carcinoma; Nature killer T-like cells; Nature killer cells; Stereotactic body radiotherapy.

MeSH terms

  • CD3 Complex
  • Carcinoma, Hepatocellular* / radiotherapy
  • Carcinoma, Hepatocellular* / surgery
  • Flow Cytometry
  • Humans
  • Killer Cells, Natural
  • Liver Neoplasms* / radiotherapy
  • Liver Neoplasms* / surgery
  • Natural Killer T-Cells*
  • Radiosurgery* / adverse effects

Substances

  • CD3 Complex