Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China.
College of Basic Medical Science, China Three Gorges University, Yichang, China.
Front Immunol. 2023 Jul 7;14:1214675. doi: 10.3389/fimmu.2023.1214675. eCollection 2023.
Lysine-specific demethylase 1 (LSD1) is an enzyme that removes lysine methylation marks from nucleosome histone tails and plays an important role in cancer initiation, progression, metastasis, and recurrence. Recent research shows that LSD1 regulates tumor cells and immune cells through multiple upstream and downstream pathways, enabling tumor cells to adapt to the tumor microenvironment (TME). As a potential anti-tumor treatment strategy, immunotherapy has developed rapidly in the past few years. However, most patients have a low response rate to available immune checkpoint inhibitors (ICIs), including anti-PD-(L)1 therapy and CAR-T cell therapy, due to a broad array of immunosuppressive mechanisms. Notably, inhibition of LSD1 turns "cold tumors" into "hot tumors" and subsequently enhances tumor cell sensitivity to ICIs. This review focuses on recent advances in LSD1 and tumor immunity and discusses a potential therapeutic strategy for combining LSD1 inhibition with immunotherapy.
赖氨酸特异性去甲基化酶 1（LSD1）是一种酶，可从核小体组蛋白尾部去除赖氨酸甲基化标记，并在癌症的起始、进展、转移和复发中发挥重要作用。最近的研究表明，LSD1 通过多个上下游途径调节肿瘤细胞和免疫细胞，使肿瘤细胞能够适应肿瘤微环境（TME）。作为一种潜在的抗肿瘤治疗策略，免疫疗法在过去几年中发展迅速。然而，由于存在广泛的免疫抑制机制，大多数患者对现有免疫检查点抑制剂（ICIs）的反应率较低，包括抗 PD-(L)1 治疗和 CAR-T 细胞治疗。值得注意的是，抑制 LSD1 可将“冷肿瘤”转变为“热肿瘤”，从而提高肿瘤细胞对 ICI 的敏感性。本综述重点介绍了 LSD1 和肿瘤免疫方面的最新进展，并讨论了 LSD1 抑制与免疫疗法联合的潜在治疗策略。
