Luteolin exerts anti-tumour immunity in hepatocellular carcinoma by accelerating CD8+ T lymphocyte infiltration

J Cell Mol Med. 2024 Sep;28(17):e18535. doi: 10.1111/jcmm.18535.

Abstract

Luteolin, a commonly used traditional Chinese medicine, has been utilized for several decades in the treatment of hepatocellular carcinoma (HCC). Previous research has demonstrated its anti-tumour efficacy, but its underlying mechanism remains unclear. This study aimed to assess the therapeutic effects of luteolin in H22 tumour-bearing mice. luteolin effectively inhibited the growth of solid tumours in a well-established mouse model of HCC. High-throughput sequencing revealed that luteolin treatment could enhance T-cell activation, cell chemotaxis and cytokine production. In addition, luteolin helped sustain a high ratio of CD8+ T lymphocytes in the spleen, peripheral blood and tumour tissues. The effects of luteolin on the phenotypic and functional changes in tumour-infiltrating CD8+ T lymphocytes were also investigated. Luteolin restored the cytotoxicity of tumour-infiltrating CD8+ T lymphocytes in H22 tumour-bearing mice. The CD8+ T lymphocytes exhibited intensified phenotype activation and increased production of granzyme B, IFN-γ and TNF-α in serum. The combined administration of luteolin and the PD-1 inhibitor enhanced the anti-tumour effects in H22 tumour-bearing mice. Luteolin could exert an anti-tumour immune response by inducing CD8+ T lymphocyte infiltration and enhance the anti-tumour effects of the PD-1 inhibitor on H22 tumour-bearing mice.

Keywords: CD8+ T lymphocyte infiltration; PD‐1 inhibitor; hepatocellular carcinoma; high‐throughput sequencing; luteolin.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes* / drug effects
  • CD8-Positive T-Lymphocytes* / immunology
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / immunology
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Granzymes / metabolism
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / immunology
  • Liver Neoplasms* / pathology
  • Luteolin* / pharmacology
  • Luteolin* / therapeutic use
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphocytes, Tumor-Infiltrating* / drug effects
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Lymphocytes, Tumor-Infiltrating* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors

Substances

  • Luteolin
  • Cytokines
  • Granzymes
  • Programmed Cell Death 1 Receptor