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。
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.
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