European Journal of Immunology (published online) New Evidence for Icaritin, a Small Molecule Discovered from a Chinese Herb by Beijing Shenogen Pharma Group, to Elicit Immunological Responses and Inhibit Tumor Growth
Recently, the renowned European Journal of Immunology published an article titled “Icaritin promotes tumor T-cell infiltration and induces antitumor immunity”. The single-molecule drug icaritin is produced by enzymatic hydrolysis of icariin, which is isolated from traditional Chinese herbal medicine Epimedium. It has both anti-inflammatory and anti-tumor activities, and a Phase III clinical trial of icaritin for treating advanced hepatocellular carcinoma is underway in China.
In this paper, both the in vitro and in vivo mechanism of the anti-tumor activity of icaritin was elucidated, and the immunomodulatory function of icaritin was explicitly demonstrated, providing a theoretical basis for the further clinical application of icaritin.
Cancer immunotherapy is an additional important approach for treating the disease along with traditional surgery, radiotherapy and chemotherapy. Tumor immunotherapy by targeted immune checkpoint inhibitors, which is represented by PD-1 antibody, has made breakthrough progress and attained significant therapeutic effect. Although small molecule immune checkpoint inhibitors have not been used in clinical practice, they have attracted extensive attention from drug developers.
In this study, icaritin effectively inhibited the growth of B16F10 melanoma and MC38 colorectal cancer cells in mice by increasing the infiltration of CD8+ T cells into tumor microenvironment and increasing the frequency of effector memory T-cells. When anti-CD8 monoclonal antibody was used to eliminate CD8+ T-cells in mice, the anti-tumor effect of icaritin disappeared, indicating that icaritin relies on CD8+ T-cells to play an anti-tumor role in cancer immunotherapy. Moreover, by analyzing the subsets of immune cells in tumor tissues, it was found that less myeloid suppressor cells (CD11b + Gr1 + MDSCs) were found in tumor microenvironment after the treatment with icaritin in mice, and PD-L1 level on MDSCs was down-regulated. Additionally, icaritin also significantly inhibited PD-L1 level in neutrophil. The paper further demonstrated that icaritin combined with PD-1 antibody or CTLA-4 antibody significantly enhanced the anti-tumor efficacy in mice compared to the treatment with PD-1 antibody and CTLA-4 antibody alone. In conclusion, the paper suggests that icaritin, as a small molecule immunomodulator, can play a similar role to that of large molecules of cancer immune checkpoint inhibition in anti-tumor immunity, this opens up a new approach for tumor immunotherapy. Furthermore, it was expected that as a small molecule drug, icaritin can combine with other immune checkpoint antibody drugs to further improve the efficacy of immunotherapy, and enhance clinical safety, accessibility and potency.