Single-intraosseous simvastatin injection suppresses cancers via activating CD8+ T cells

Abstract

Immunotherapies provide effective strategies for cancer treatment. Cholesterol induces CD8+ T cell exhaustion, which inhibits antitumor immunity. CD8+ T cells are derived from bone marrow and transport and function in bone marrow, where provides more porous cavities for drugs to access the circulation than other solid organs. We previously found that single-dose intraosseous (i.o.) injection of simvastatin suppresses breast cancer development and prolongs survival, but the exact mechanism remains unclear. In this study, we found the antitumor activity of simvastatin i.o. mainly depended on CD8+ T cells. Simvastatin i.o. increased the percentage and cytotoxicity of CD8+ T cells and downregulated the expression of PD-1, TIM3 and CTLA4 in CD8+ T cells in vivo. Simvastatin promoted the activation, proliferation and cytotoxicity of tumor antigen-specific CD8+ T cells in vitro. Furthermore, Simvastatin i.o. suppressed cancers by activating the T-cell antigen receptor signaling pathway. Taken together, simvastatin i.o. effectively suppresses cancer progression, which would be a potential strategy for cancer treatment.

Keywords

• Simvastatin
• Intraosseous injection
• Cancer
• CD8+ T cells
• T cell antigen receptor signaling pathway