Ren Yongjing, Gong Yanan, Zhao Huan, You Duo, Li Zhifei, Wang Sai-Qi, Chen Xiaobing
Department of Oncology, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer and Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer, Zhengzhou 450008, China.
Chinese Medicine Academy of Chinese Medicine sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Chin J Cancer Res. 2024 Dec 30;36(6):669-682. doi: 10.21147/j.issn.1000-9604.2024.06.06.
Gastric cancer (GC) ranks 3rd in incidence rate and mortality rate among malignant tumors in China, and the age-standardized five-year net survival rate of patients with GC was 35.9% from 2010 to 2014. The tumor immune microenvironment (TIME), which includes T cells, macrophages, natural killer (NK) cells and B cells, significantly affects tumor progression, immunosuppression and drug resistance in patients with GC. In recent years, immunotherapy has become the first-line or second-line treatment for GC. Lysine-specific demethylase 1 (LSD1, also known as KDM1A) was the first identified human histone demethylase, and high expression of LSD1 in GC is closely related to the dysfunction of the above types of immune cells. Therefore, LSD1 inhibitors could regulate the cytotoxic effects of immune cells against tumor cells through a variety of mechanisms to control tumor progression. In this review, we discuss the effects of LSD1 inhibitors on immune cells in GC and propose LSD1 as a new potential target for immunotherapy in GC.
胃癌(GC)在中国恶性肿瘤的发病率和死亡率中排名第三,2010年至2014年期间,GC患者的年龄标准化五年净生存率为35.9%。肿瘤免疫微环境(TIME)包括T细胞、巨噬细胞、自然杀伤(NK)细胞和B细胞,显著影响GC患者的肿瘤进展、免疫抑制和耐药性。近年来,免疫疗法已成为GC的一线或二线治疗方法。赖氨酸特异性去甲基化酶1(LSD1,也称为KDM1A)是首个被鉴定出的人类组蛋白去甲基化酶,GC中LSD1的高表达与上述类型免疫细胞的功能障碍密切相关。因此,LSD1抑制剂可通过多种机制调节免疫细胞对肿瘤细胞的细胞毒性作用,以控制肿瘤进展。在本综述中,我们讨论了LSD1抑制剂对GC中免疫细胞的影响,并提出LSD1作为GC免疫治疗的新潜在靶点。