Luteolin exerts anti-tumor immunity in hepatocellular carcinoma by accelerating CD8+ T lymphocyte infiltration
We observed that luteolin effectively restrained the growth of solid tumors in the established mouse model of HCC. Expression spectrum chip sequencing showed that treatment with luteolin could promote T cell activation, cell chemotaxis and cytokine production. Furthermore, we explored the influence of luteoin on the phenotypic and functional alterations of T cells. Our findings revealed that luteolin maintained a high ratio of CD8+ T cells in the peripheral blood, spleen, and tumor tissues. Additionally, luteolin restored the cytotoxicity of tumor-infiltrating CD8+ T cells in H22 tumor-bearing mice. Moreover, CD8+ T cells showed stronger activation phenotypes and more production of IFN-?, TNFa, and Granzyme B in serum. Furthermore, the co-administration of luteolin and PD-1 mAb resulted in potentiated anti-tumor effects in H22 tumor-bearing mice.These findings indicate that luteolin could exert an anti-tumor immune response by inducing CD8+ T cell infiltration and enhance the anti-tumor effects of PD-1 mAb in HCC treatment in H22 tumor-bearing mice. Overall design: To investigate the function of luteolin on hepatocellular carcinoma, H22 cells were injected subcutaneously into BALB/c mice.200mg/kg luteolin or 0.5% carboxymethyl cellulose sodium were administered strictly once daily for 21 days in a volume of 0.2 ml when the tumor volume reached ~50 mm3.  We then performed gene expression profiling analysis using data obtained from RNA-seq .