Hydroxypropyl-β-cyclodextrin inhibits the development of triple negative breast cancer by enhancing antitumor immunity

Abstract

Abstract Triple negative breast cancer (TNBC) is a most aggressive type of breast cancer without effective therapies. Cyclodextrin, a cyclic oligosaccharide is used as drug delivery carrier with cholesterol lowering property. However, whether cyclodextrin can inhibit the proliferation and migration of TNBC as well as the underlying mechanisms are unclear. In the present study, we demonstrated that 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) inhibited the growth and metastasis of TNBC both in vitro and in vivo. Meanwhile, the antitumor effects of HP-β-CD were also observed in a mouse melanoma model. Mechanistically, we initially determined that cholesterol supplementation can attenuate HP-b-CD-inhibited TNBC growth and metastasis both in vitro and in vivo. In vivo, HP-β-CD promoted the infiltration of T cells into the tumor microenvironment (TME) and improved exhaustion of CD8+ T cells via reducing endoplasmic reticulum (ER) stress and immune checkpoint molecules. Additionally, HP-β-CD inhibited the recruitment of tumor associated macrophages to the TME via reducing CCL2-p38MAPK-NF-kB axis. HP-β-CD also inhibited the epithelial mesenchymal transition (EMT) of TNBC cells mediated by transforming growth factor-b (TGF-b) signaling pathway. In summary, the data in the current study suggest that HP-β-CD effectively inhibited proliferation and metastasis of TNBC and melanoma, highlighting HP-β-CD may be a potential general antitumor clinical drug.