基于胆固醇代谢调控的肿瘤免疫治疗新方法

 免疫检测点阻断疗法等肿瘤免疫疗法近年在临床上取得了重大突破，但仍存在响应率低等显著缺点，需开发新的肿瘤免疫疗法以使更多肿瘤患者受益。胆固醇作为细胞质膜脂质的重要组成成分，其代谢可以影响T细胞的质膜环境及效应功能。本研究发现，通过调控胆固醇代谢可以增强CD8⁺ T细胞的抗肿瘤免疫反应。抑制关键胆固醇酯化酶ACAT1的活性，CD8⁺ T细胞质膜游离胆固醇水平上调，细胞的抗肿瘤免疫应答显著增强，这为肿瘤免疫治疗提供了新思路和新方法。

A new cancer immunotherapy based on cholesterol metabolism modulation

Immune checkpoint blockade and other cancer immunotherapies have achieved great success in clinic but problems such as low response rate still remain. Cholesterol is a key component of cell membrane, whose cellular metabolism can influence the plasma membrane environment and effector function of T cells. We have found that the anti-tumor immune response of CD8⁺ T cells can be potentiated by modulating cellular cholesterol metabolism. Inhibiting the activity of ACAT1, a key cholesterol esterification enzyme, can upregulate the cholesterol level on CD8⁺ T cell plasma membrane, and significantly enhance the anti-tumor effector function. This finding provides a new method for cancer immunotherapy.