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. 2019 Dec;49(12):2235-2244.
doi: 10.1002/eji.201948225. Epub 2019 Sep 18.

Icaritin promotes tumor T-cell infiltration and induces antitumor immunity in mice

Haibang Hao  1   2 , Qi Zhang  2 , Hai Zhu  2 , Yuxiang Wen  1 , Ding Qiu  1 , Jian Xiong  1 , Xiaolan Fu  1 , Yuzhang Wu  1 , Kun Meng  2 , Jian Li  1
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Free article

Icaritin promotes tumor T-cell infiltration and induces antitumor immunity in mice

Haibang Hao et al. Eur J Immunol. 2019 Dec.
Free article

Abstract

Icaritin, a hydrolytic product of icariin isolated from traditional Chinese herbal medicine genus Epimedium, has many pharmacological and biological activities. Here, we show that icaritin can effectively decrease tumor burden of murine B16F10 melanoma and MC38 colorectal tumors in a T-cell dependent manner. The treatment effects are associated with increased CD8 T-cell infiltration and increased effector memory T-cell frequency. In vivo depletion of CD8 T cell using an anti-CD8 monoclonal antibody abolished the antitumor effect, which supports the critical role of CD8 T cells during icaritin treatment. By analyzing immune cells in the tumor tissue, we found reduced frequency of CD11b+ Gr1+ myeloid-derived suppression cells (MDSCs) infiltration and downregulation of PD-L1 expression on MDSCs after icaritin treatment. This was not limited to MDSCs, as icaritin also decreased the expression of PD-L1 on neutrophils. Importantly, the combination of anti-PD-1/CTLA-4 and icaritin significantly enhances antitumor ability and increases the efficacy of either treatment alone. Our findings reveal that icaritin induces antitumor immunity in a CD8 T-cell-dependent way and justify further investigation of combining immune checkpoint therapy to icaritin-based antitumor therapy.

Keywords: CD8 T-cells accumulation; Combination immunotherapy; Icaritin; MDSCs; Melanoma.

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References

    1. Wang, Z., Zhang, X., Wang, H., Qi, L. and Lou, Y., Neuroprotective effects of icaritin against beta amyloid-induced neurotoxicity in primary cultured rat neuronal cells via estrogen-dependent pathway. Neuroscience 2007. 145: 911-922.
    1. Zhang, W., Xing, B., Yang, L., Shi, J. and Zhou, X., Icaritin attenuates myocardial ischemia and reperfusion injury via anti-inflammatory and anti-oxidative stress effects in rats. Am. J. Chin. Med. 2015. 43: 1083-1097.
    1. Qin, L., Yao, D., Zheng, L., Liu, W. C., Liu, Z., Lei, M., Huang, L. et al., Phytomolecule icaritin incorporated PLGA/TCP scaffold for steroid-associated osteonecrosis: proof-of-concept for prevention of hip joint collapse in bipedal emus and mechanistic study in quadrupedal rabbits. Biomaterials 2015. 59: 125-143.
    1. Yao, D., Xie, X. H., Wang, X. L., Wan, C., Lee, Y. W., Chen, S. H., Pei, D. Q. et al., Icaritin, an exogenous phytomolecule, enhances osteogenesis but not angiogenesis-an in vitro efficacy study. PLoS One. 2012. 7: e41264.
    1. Zhou, C., Chen, Z., Lu, X., Wu, H., Yang, Q. and Xu, D., Icaritin activates JNK-dependent mPTP necrosis pathway in colorectal cancer cells. Tumour Biol. 2016. 37: 3135-3144.

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