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.

免疫疗法为癌症治疗提供了有效的策略。胆固醇诱导 CD8 ⁺ T 细胞耗竭，从而抑制抗肿瘤免疫。CD8 ⁺ T 细胞来源于骨髓并在骨髓中运输和发挥作用，与其他实体器官相比，骨髓为药物进入循环提供了更多的多孔腔。我们之前发现单剂量骨内 (io) 注射辛伐他汀可抑制乳腺癌的发展并延长生存期，但确切的机制仍不清楚。在本研究中，我们发现辛伐他汀的抗肿瘤活性主要依赖于CD8 ⁺ T细胞。辛伐他汀 io 增加 CD8 ^{+的百分比和细胞毒性}T 细胞并下调 CD8 ⁺ T 细胞中PD-1、TIM3 和 CTLA4 的表达。辛伐他汀在体外促进肿瘤抗原特异性CD8 ⁺ T细胞的活化、增殖和细胞毒性。此外，辛伐他汀 io 通过激活 T 细胞抗原受体信号通路来抑制癌症。总之，辛伐他汀 io 有效抑制癌症进展，这将是癌症治疗的潜在策略。